xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06022939</url>
    </required_header>
    <id_info>
      <org_study_id>S2213</org_study_id>
      <secondary_id>NCI-2023-04234</secondary_id>
      <secondary_id>S2213</secondary_id>
      <secondary_id>S2213</secondary_id>
      <secondary_id>U10CA180888</secondary_id>
      <nct_id>NCT06022939</nct_id>
    </id_info>
    <brief_title>Comparing Dara-VCD Chemotherapy Plus Stem Cell Transplant to Dara-VCD Chemotherapy Alone for People Who Have Newly Diagnosed AL Amyloidosis</brief_title>
    <official_title>A Phase III, Randomized Study of Daratumumab, Cyclophosphamide, Bortezomib and Dexamethasone (Dara-VCD) Induction Followed by Autologous Stem Cell Transplant or Dara-VCD Consolidation and Daratumumab Maintenance in Patients With Newly Diagnosed AL Amyloidosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>SWOG Cancer Research Network</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>SWOG Cancer Research Network</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase III trial compares the effect of adding a stem cell transplant with melphalan&#xD;
        after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and&#xD;
        dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with&#xD;
        newly diagnosed amyloid light chain (AL) amyloidosis. Melphalan is a chemotherapy given prior&#xD;
        to a stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant&#xD;
        helps kill cancer cells in the body and helps make room in the patient's bone marrow for new&#xD;
        blood-forming cells (stem cells) to grow. The stem cells are then returned to the patients to&#xD;
        replace the blood forming cells that were destroyed by the chemotherapy. Daratumumab is in a&#xD;
        class of medications called monoclonal antibodies. It binds to a protein called CD38, which&#xD;
        is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab&#xD;
        may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs, such as&#xD;
        cyclophosphamide and bortezomib, work in different ways to stop the growth of cancer cells,&#xD;
        either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
        spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to&#xD;
        lower the body's immune response to help stop the growth of cancer cells. Giving a stem cell&#xD;
        transplant with melphalan after Dara-VCD may kill more cancer cells in patients with newly&#xD;
        diagnosed AL amyloidosis.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To compare major organ deterioration progression-free survival between participants&#xD;
        randomized to the autologous stem cell transplant (ASCT) and non-ASCT arms of this study.&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT&#xD;
        arms of this study.&#xD;
  &#xD;
        II. To compare rates of cardiac and renal organ responses between participants randomized to&#xD;
        the ASCT and non-ASCT arms of this study.&#xD;
  &#xD;
        III. To compare rates of cardiac and renal organ progression between participants randomized&#xD;
        to the ASCT and non-ASCT arms of the study.&#xD;
  &#xD;
        IV. To compare the frequency and severity of toxicities between participants randomized to&#xD;
        the ASCT and non-ASCT arms of this study.&#xD;
  &#xD;
        V. To compare minimal residual disease (MRD) negativity rates between participants randomized&#xD;
        to the ASCT and non-ACST arms of this study.&#xD;
  &#xD;
        ADDITIONAL OBJECTIVES:&#xD;
  &#xD;
        I. To compare the best overall hematologic response rates between participants randomized to&#xD;
        the ASCT and non-ASCT arms of this study.&#xD;
  &#xD;
        II. To compare rates of hematologic complete response (CR) and very good partial response,&#xD;
        following completion of consolidation therapy between participants randomized to the ASCT and&#xD;
        non-ASCT arms of this study, post-consolidation.&#xD;
  &#xD;
        III. To compare hematologic progression-free survival between participants randomized to the&#xD;
        ASCT and non-ASCT arms of this study.&#xD;
  &#xD;
        IV. To compare time to next treatment between participants randomized to the ASCT and&#xD;
        non-ASCT arms of the study.&#xD;
  &#xD;
        V. To evaluate utilization of delayed ASCT in participants randomized to the non-ASCT arm of&#xD;
        the study.&#xD;
  &#xD;
        TRANSLATIONAL MEDICINE PRIMARY OBJECTIVES:&#xD;
  &#xD;
        I. To compare MRD negativity rates from bone marrow aspirates via next generation flow&#xD;
        cytometry (NGF) between the ASCT and non-ASCT arms of this study post-consolidation.&#xD;
  &#xD;
        II. To bank specimens for future use.&#xD;
  &#xD;
        TRANSLATIONAL MEDICINE EXPLORATORY OBJECTIVES:&#xD;
  &#xD;
        I. To evaluate MRD negativity rates at post-induction, and compare MRD negativity rates at 12&#xD;
        months post-consolidation from bone marrow aspirates via NGF between participants randomized&#xD;
        to the ASCT and non-ASCT arms of this study.&#xD;
  &#xD;
        II. To investigate the association of achieving MRD negativity at any point (post-induction,&#xD;
        post-consolidation, or 12 months post-consolidation) via NGF from bone marrow aspirates with&#xD;
        major organ deterioration-progression free survival (MOD-PFS).&#xD;
  &#xD;
        III. To investigate the association of achieving sustained MRD negativity (MRD negative at&#xD;
        two consecutive measurements -- post-induction, post-consolidation, and 12 months&#xD;
        post-consolidation) via NGF from bone marrow aspirates with MOD-PFS.&#xD;
  &#xD;
        QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To compare patient-reported physical function following consolidation treatment between&#xD;
        participants randomized to the ASCT and non-ASCT arms using the Patient Reported Outcomes&#xD;
        Measurement Information System (PROMIS)-29+2 Profile version (v) 2.1 physical function&#xD;
        sub-scale.&#xD;
  &#xD;
        QOL SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To compare patient-reported fatigue following consolidation treatment between participants&#xD;
        randomized to the ASCT and non-ASCT arms using the PROMIS-29 fatigue subscale.&#xD;
  &#xD;
        II. To compare longitudinal changes in physical function using the PROMS-29+2 between&#xD;
        participants randomized to the ASCT and non-ASCT arms.&#xD;
  &#xD;
        QOL EXPLORATORY OBJECTIVES:&#xD;
  &#xD;
        I. To assess baseline symptom burden in AL amyloidosis patients prior to induction therapy&#xD;
        using the PROMIS-29+2.&#xD;
  &#xD;
        II. To compare mean scores of symptom scales using the PROMIS-29+2 following consolidation&#xD;
        treatment, and at 6 months and 12 months from step 3 registration between treatment arms.&#xD;
  &#xD;
        III. To compare mean scores of functional scales using the PROMIS-29+2, following&#xD;
        consolidation treatment, and at 6 months and 12 months from step 3 registration between&#xD;
        treatment arms.&#xD;
  &#xD;
        IV. To explore whether longitudinal changes in symptoms, functioning, and overall heath&#xD;
        related quality of life (HRQoL) as assessed by the PROMIS-29 +2 (version 2.1) differ&#xD;
        according to treatment group and, separately, according to baseline cardiac or renal&#xD;
        involvement using interaction tests between participants randomized to the ASCT and non-ASCT&#xD;
        arms.&#xD;
  &#xD;
        V. To compare health utility indices using the PROMIS preference score (PROPr) between&#xD;
        patients randomized to the ASCT and non-ASCT arms.&#xD;
  &#xD;
        PATIENT REPORTED OUTCOME (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) PRIMARY&#xD;
        OBJECTIVE:&#xD;
  &#xD;
        I. To compare patient reported symptoms regarding treatment emergent adverse events of&#xD;
        interest using the Patient Reported Outcome CTCAE (PRO-CTCAE) Measurement System between&#xD;
        patients randomized to the ASCT and non-ASCT arms of this study.&#xD;
  &#xD;
        OUTLINE:&#xD;
  &#xD;
        INDUCTION: Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) over 3-5&#xD;
        minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients&#xD;
        receive bortezomib SC over 3-5 minutes, cyclophosphamide orally (PO) or intravenously (IV),&#xD;
        and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days&#xD;
        for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients&#xD;
        undergo computed tomography (CT), magnetic resonance imaging (MRI) or positron emission&#xD;
        tomography (PET)-CT and fat pad aspiration at screening. Patients undergo echocardiography at&#xD;
        screening, the completion of induction, and at progression. Patients undergo bone marrow&#xD;
        aspiration and biopsy at screening, post induction treatment and at progression. Patients&#xD;
        undergo blood and urine sample collection at screening, at the start of each cycle, and the&#xD;
        end of treatment and during follow up or at progression.&#xD;
  &#xD;
        CONSOLIDATION: Patients who achieve an overall response of partial response or better after 3&#xD;
        cycles of Dara-VCD are randomized to 1 of 2 arms.&#xD;
  &#xD;
        ARM I: Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and&#xD;
        15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO&#xD;
        or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles&#xD;
        in the absence of disease progression or unacceptable toxicity. Patients undergo&#xD;
        echocardiography at screening and at progression. Patients undergo bone marrow aspiration and&#xD;
        biopsy within14-28 days post consolidation treatment and at progression. Patients undergo&#xD;
        blood and urine sample collection at screening, at the start of each cycle, and the end of&#xD;
        treatment and during follow up or at progression.&#xD;
  &#xD;
        ARM II: Patients undergo collection of peripheral blood stem cells. Patients receive&#xD;
        melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the&#xD;
        absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at&#xD;
        screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90&#xD;
        days post initiation of stem cell transplant. Patients undergo blood and urine sample&#xD;
        collection at screening, during treatment, and the end of treatment and during follow up or&#xD;
        at progression.&#xD;
  &#xD;
        MAINTENANCE: Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5&#xD;
        minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence&#xD;
        of disease progression or unacceptable toxicity. Patients undergo echocardiography at&#xD;
        screening, 12 months post consolidation treatment and at progression. Patients undergo bone&#xD;
        marrow aspiration and biopsy 12 months post consolidation treatment and at progression.&#xD;
        Patients undergo blood and urine sample collection at screening, during treatment, 12 months&#xD;
        post consolidation treatment and during follow up or at progression.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up every 3 or 6 months up to 4&#xD;
        years after registration.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 31, 2023</start_date>
    <completion_date type="Anticipated">October 29, 2030</completion_date>
    <primary_completion_date type="Anticipated">July 29, 2030</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Major organ deterioration progression-free survival (PFS)</measure>
      <time_frame>From date of randomization (Step 2 registration) to date of first documentation of hematologic progression, cardiac organ progression, renal organ progression, or death due to any cause, assessed up to 4 years</time_frame>
      <description>Will be performed using a stratified log-rank test for comparison between study arms. The analyses will be stratified according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 versus [vs.] 2-3), hematological response following 2 cycles of daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) induction (partial response [PR] or worse vs. very good partial response [VGPR] or better), and presence of t(11;14) by interphase fluorescence in situ hybridization [iFISH] (yes vs. no). All eligible participants will be considered in analyses of the primary endpoint, according to their assigned arm at randomization.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>From randomization to date of death due to any cause, assessed up to 4 years</time_frame>
      <description>Will be performed using a stratified log-rank test for comparison between arms, with stratification according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. [VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hematologic PFS</measure>
      <time_frame>From randomization (Step 2 registration) to date of first documentation of hematologic progression, or death due to any cause, assessed up to 4 years</time_frame>
      <description>Will be performed using a stratified log-rank test for comparison between arms, with stratification according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiac and renal organ response rates</measure>
      <time_frame>Up to 4 years</time_frame>
      <description>Progression will be defined based on objective evidence of worsening of organ dysfunction due to AL amyloid. Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurable residual disease (MRD) negativity rate</measure>
      <time_frame>From baseline to off treatment follow-up (prior to progression) or 12 months post consolidation</time_frame>
      <description>Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Best overall hematologic response</measure>
      <time_frame>From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years</time_frame>
      <description>Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall hematologic response rate</measure>
      <time_frame>From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years</time_frame>
      <description>Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of complete response</measure>
      <time_frame>Up to 4 years</time_frame>
      <description>Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of very good complete response or better</measure>
      <time_frame>Up to 4 years</time_frame>
      <description>Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to next treatment</measure>
      <time_frame>From date of initial registration (Step 1) to date of initiation of next line of therapy, assessed up to 4 years</time_frame>
      <description>Will be analyzed using the cumulative incidence competing risks method.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in patient reported health quality of life (QOL)</measure>
      <time_frame>From baseline to post-maintenance, approximately 24 months</time_frame>
      <description>Will use the PROMIS-29+2 (version 2.1) to compare the physical function between participants in the ASCT vs. non-ASCT arm.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to the end of maintenance therapy, approximately 24 months</time_frame>
      <description>Participant-reported toxicity will be examined using Patient Reported Outcome-Common Terminology Criteria for Adverse Events.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Bone marrow Next Generation Flow based MRD negativity rates</measure>
      <time_frame>At the end of consolidation, approximately 6 months</time_frame>
      <description>Comparisons of MRD negativity rates between arms will be made using a stratified Cochran-Mantel-Haenszel test, with analyses stratified according to European modification of the Mayo Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3a), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 physical function domain</measure>
      <time_frame>From baseline to post-consolidation, approximately 6 months</time_frame>
      <description>Analysis will be conducted using multiple linear regression analysis, adjusting for the clinical study-specified stratification factors (which are also anticipated to influence QOL endpoints), and the baseline score as covariates.</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in PROMIS-29 fatigue domain score</measure>
      <time_frame>From baseline to post-consolidation, approximately 6 months</time_frame>
      <description>Analysis will be conducted using linear regression, adjusting for the clinical study-specified stratification factors and the baseline PROMIS-29 fatigue domain score as covariates. Additionally, will conduct longitudinal modeling of the physical function domain score over time (through 12 months from registration Step 3). For longitudinal modeling, linear mixed models will be used.</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">338</enrollment>
    <condition>AL Amyloidosis</condition>
    <arm_group>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI or PET-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Autologous Hematopoietic Stem Cell Transplantation</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <other_name>AHSCT</other_name>
      <other_name>Autologous</other_name>
      <other_name>Autologous Hematopoietic Cell Transplantation</other_name>
      <other_name>Autologous Stem Cell Transplant</other_name>
      <other_name>Autologous Stem Cell Transplantation</other_name>
      <other_name>Stem Cell Transplantation, Autologous</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biopsy</intervention_name>
      <description>Undergo fat pad biopsy</description>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>BIOPSY_TYPE</other_name>
      <other_name>Bx</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood and urine specimen collection</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Marrow Aspiration</intervention_name>
      <description>Undergo bone marrow aspiration</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Bone Marrow Biopsy</intervention_name>
      <description>Undergo bone marrow biopsy</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
      <other_name>Biopsy of Bone Marrow</other_name>
      <other_name>Biopsy, Bone Marrow</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bortezomib</intervention_name>
      <description>Given SC</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid</other_name>
      <other_name>LDP 341</other_name>
      <other_name>MLN341</other_name>
      <other_name>PS-341</other_name>
      <other_name>PS341</other_name>
      <other_name>Velcade</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT scan</description>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>Given PO or IV</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>(-)-Cyclophosphamide</other_name>
      <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
      <other_name>Carloxan</other_name>
      <other_name>Ciclofosfamida</other_name>
      <other_name>Ciclofosfamide</other_name>
      <other_name>Cicloxal</other_name>
      <other_name>Clafen</other_name>
      <other_name>Claphene</other_name>
      <other_name>CP monohydrate</other_name>
      <other_name>CTX</other_name>
      <other_name>CYCLO-cell</other_name>
      <other_name>Cycloblastin</other_name>
      <other_name>Cycloblastine</other_name>
      <other_name>Cyclophospham</other_name>
      <other_name>Cyclophosphamid monohydrate</other_name>
      <other_name>Cyclophosphamide Monohydrate</other_name>
      <other_name>Cyclophosphamidum</other_name>
      <other_name>Cyclophosphan</other_name>
      <other_name>Cyclophosphane</other_name>
      <other_name>Cyclophosphanum</other_name>
      <other_name>Cyclostin</other_name>
      <other_name>Cyclostine</other_name>
      <other_name>Cytophosphan</other_name>
      <other_name>Cytophosphane</other_name>
      <other_name>Cytoxan</other_name>
      <other_name>Fosfaseron</other_name>
      <other_name>Genoxal</other_name>
      <other_name>Genuxal</other_name>
      <other_name>Ledoxina</other_name>
      <other_name>Mitoxan</other_name>
      <other_name>Neosar</other_name>
      <other_name>Revimmune</other_name>
      <other_name>Syklofosfamid</other_name>
      <other_name>WR- 138719</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Daratumumab and Hyaluronidase-fihj</intervention_name>
      <description>Given SC</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
      <other_name>DARA Co-formulated with rHuPH20</other_name>
      <other_name>DARA/rHuPH20</other_name>
      <other_name>Daratumumab + rHuPH20</other_name>
      <other_name>Daratumumab with rHuPH20</other_name>
      <other_name>Daratumumab-rHuPH20</other_name>
      <other_name>Daratumumab/Hyaluronidase-fihj</other_name>
      <other_name>Daratumumab/rHuPH20 Co-formulation</other_name>
      <other_name>Darzalex Faspro</other_name>
      <other_name>Darzalex/rHuPH20</other_name>
      <other_name>HuMax-CD38-rHuPH20</other_name>
      <other_name>Recombinant Human Hyaluronidase Mixed with Daratumumab</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dexamethasone</intervention_name>
      <description>Given PO or IV</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>Aacidexam</other_name>
      <other_name>Adexone</other_name>
      <other_name>Aknichthol Dexa</other_name>
      <other_name>Alba-Dex</other_name>
      <other_name>Alin</other_name>
      <other_name>Alin Depot</other_name>
      <other_name>Alin Oftalmico</other_name>
      <other_name>Amplidermis</other_name>
      <other_name>Anemul mono</other_name>
      <other_name>Auricularum</other_name>
      <other_name>Auxiloson</other_name>
      <other_name>Baycadron</other_name>
      <other_name>Baycuten</other_name>
      <other_name>Baycuten N</other_name>
      <other_name>Cortidexason</other_name>
      <other_name>Cortisumman</other_name>
      <other_name>Decacort</other_name>
      <other_name>Decadrol</other_name>
      <other_name>Decadron</other_name>
      <other_name>Decadron DP</other_name>
      <other_name>Decalix</other_name>
      <other_name>Decameth</other_name>
      <other_name>Decasone R.p.</other_name>
      <other_name>Dectancyl</other_name>
      <other_name>Dekacort</other_name>
      <other_name>Deltafluorene</other_name>
      <other_name>Deronil</other_name>
      <other_name>Desamethasone</other_name>
      <other_name>Desameton</other_name>
      <other_name>Dexa-Mamallet</other_name>
      <other_name>Dexa-Rhinosan</other_name>
      <other_name>Dexa-Scheroson</other_name>
      <other_name>Dexa-sine</other_name>
      <other_name>Dexacortal</other_name>
      <other_name>Dexacortin</other_name>
      <other_name>Dexafarma</other_name>
      <other_name>Dexafluorene</other_name>
      <other_name>Dexalocal</other_name>
      <other_name>Dexamecortin</other_name>
      <other_name>Dexameth</other_name>
      <other_name>Dexamethasone Intensol</other_name>
      <other_name>Dexamethasonum</other_name>
      <other_name>Dexamonozon</other_name>
      <other_name>Dexapos</other_name>
      <other_name>Dexinoral</other_name>
      <other_name>Dexone</other_name>
      <other_name>Dinormon</other_name>
      <other_name>Dxevo</other_name>
      <other_name>Fluorodelta</other_name>
      <other_name>Fortecortin</other_name>
      <other_name>Gammacorten</other_name>
      <other_name>Hemady</other_name>
      <other_name>Hexadecadrol</other_name>
      <other_name>Hexadrol</other_name>
      <other_name>Lokalison-F</other_name>
      <other_name>Loverine</other_name>
      <other_name>Methylfluorprednisolone</other_name>
      <other_name>Millicorten</other_name>
      <other_name>Mymethasone</other_name>
      <other_name>Orgadrone</other_name>
      <other_name>Spersadex</other_name>
      <other_name>TaperDex</other_name>
      <other_name>Visumetazone</other_name>
      <other_name>ZoDex</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Echocardiography</intervention_name>
      <description>Undergo echocardiography</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
      <other_name>EC</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Magnetic Resonance Imaging</intervention_name>
      <description>Undergo MRI</description>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>Magnetic Resonance</other_name>
      <other_name>Magnetic resonance imaging (procedure)</other_name>
      <other_name>Magnetic Resonance Imaging Scan</other_name>
      <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
      <other_name>MR</other_name>
      <other_name>MR Imaging</other_name>
      <other_name>MRI</other_name>
      <other_name>MRI Scan</other_name>
      <other_name>NMR Imaging</other_name>
      <other_name>NMRI</other_name>
      <other_name>Nuclear Magnetic Resonance Imaging</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Melphalan</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <other_name>Alanine Nitrogen Mustard</other_name>
      <other_name>CB-3025</other_name>
      <other_name>L-PAM</other_name>
      <other_name>L-Phenylalanine Mustard</other_name>
      <other_name>L-Sarcolysin</other_name>
      <other_name>L-Sarcolysin Phenylalanine mustard</other_name>
      <other_name>L-Sarcolysine</other_name>
      <other_name>Melphalanum</other_name>
      <other_name>Phenylalanine Mustard</other_name>
      <other_name>Phenylalanine Nitrogen Mustard</other_name>
      <other_name>Sarcoclorin</other_name>
      <other_name>Sarkolysin</other_name>
      <other_name>WR-19813</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Positron Emission Tomography</intervention_name>
      <description>Undergo PET-CT</description>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <other_name>Medical Imaging, Positron Emission Tomography</other_name>
      <other_name>PET</other_name>
      <other_name>PET Scan</other_name>
      <other_name>Positron emission tomography (procedure)</other_name>
      <other_name>Positron Emission Tomography Scan</other_name>
      <other_name>Positron-Emission Tomography</other_name>
      <other_name>proton magnetic resonance spectroscopic imaging</other_name>
      <other_name>PT</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Stem Cell Isolation</intervention_name>
      <description>Undergo stem cell collection</description>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <other_name>Isolation, Stem Cell</other_name>
      <other_name>Stem Cell Collection</other_name>
      <other_name>Stem Cell Recovery</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Survey Administration</intervention_name>
      <description>Ancillary study</description>
      <arm_group_label>Consolidation Arm I (Chemotherapy)</arm_group_label>
      <arm_group_label>Consolidation Arm II (Chemotherapy, ASCT)</arm_group_label>
      <arm_group_label>Induction (Chemotherapy)</arm_group_label>
      <arm_group_label>Maintenance (daratumumab and hyaluronidase-fihj)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  STEP 1: Participants must have systemic AL amyloidosis which is biopsy proven and&#xD;
               includes histologically-confirmed by positive Congo red stain with green birefringence&#xD;
               on polarized light microscopy, OR characteristic appearance by electron microscopy AND&#xD;
               confirmatory AL amyloid typing (mass spectrometry-based proteomic analysis or&#xD;
               immunofluorescence). If there is question regarding diagnosis, consult study chairs&#xD;
               prior to registration&#xD;
  &#xD;
            -  STEP 1: Participants must have measurable disease within 28 days prior to treatment if&#xD;
               initiated prior to registration or within 28 days of registration as defined by at&#xD;
               least one of the following:&#xD;
  &#xD;
                 -  Positive monoclonal serum immunofixation electrophoresis&#xD;
  &#xD;
                 -  Positive monoclonal urine immunofixation electrophoresis&#xD;
  &#xD;
                 -  Monoclonal plasma cells in bone marrow In addition, participants must also have a&#xD;
                    difference between the involved and uninvolved free light chain (dFLC) &gt;= 2 mg/dL&#xD;
  &#xD;
            -  STEP 1: Participants may receive up to one cycle (or 28 days) of therapy prior to&#xD;
               enrollment. If a patient receives &gt;= 75% of 1 cycle of protocol identical Dara-VCD,&#xD;
               this will be considered 1 cycle of protocol induction. Any patient who receives less&#xD;
               than 75% of 1 cycle of Dara-VCD or non-protocol therapy will still be eligible but&#xD;
               will be treated per protocol. If protocol identical therapy is initiated prior to&#xD;
               enrollment, this treatment is not continued but rather treatment is dictated per&#xD;
               protocol&#xD;
  &#xD;
            -  STEP 1: Participants may be receiving chronic corticosteroids if they are being given&#xD;
               for disorders other than AL amyloidosis or myeloma&#xD;
  &#xD;
            -  STEP 1: Participant must be &gt;= 18 years old&#xD;
  &#xD;
            -  STEP 1: Participant must have Eastern Cooperative Oncology Group (ECOG) performance&#xD;
               score (PS) of 0, 1, or 2 (PS = 3 may be allowed if secondary to neuropathy)&#xD;
  &#xD;
            -  STEP 1: Participant must have a complete medical history and physical exam within 28&#xD;
               DAYS prior to registration&#xD;
  &#xD;
            -  STEP 1: Participants must be willing to undergo high dose chemotherapy and autologous&#xD;
               stem cell transplantation if they are randomized to the arm receiving high dose&#xD;
               chemotherapy and autologous stem cell transplantation&#xD;
  &#xD;
            -  STEP 1: Participants must be eligible to receive high dose chemotherapy with melphalan&#xD;
               at a dose of 200 mg/m^2 or 140 mg/m^2 (200 mg/m^2 is highly encouraged but not&#xD;
               mandated). Transplant eligibility criteria are included in the general eligibility&#xD;
               criteria listed below:&#xD;
  &#xD;
                 -  Participant must have a supine systolic blood pressure (BP) &gt;= 90 mmHg (at&#xD;
                    registration step-1, this may by supported by midodrine&#xD;
  &#xD;
                 -  Participant must have non-severe cardiac AL (meeting all the below criteria) as&#xD;
                    defined by:&#xD;
  &#xD;
                      -  N-terminal proB-type natriuretic peptide (NT proBNP) &lt; 5000 (if no NTproBNP,&#xD;
                         brain natriuretic peptide [BNP] must be available and &lt; 400)&#xD;
  &#xD;
                      -  Troponin T (TnT) &lt; 0.06. If not available, one of the following two criteria&#xD;
                         must be met:&#xD;
  &#xD;
                           -  High sensitivity troponin (hsTnT) T &lt; 75 or troponin I &lt; 0.1ng/dL&#xD;
  &#xD;
                      -  New York Heart Association (NYHA) I or II&#xD;
  &#xD;
                      -  Cardiac ejection fraction (EF) &gt;= 40%&#xD;
  &#xD;
            -  STEP 1: Hemoglobin &gt;= 8.0 g/dL (&gt; 5 mmol/L); red blood cell transfusion allowed up to&#xD;
               7 day prior to registration (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support granulocyte colony-stimulating factor [G-CSF] is permitted per&#xD;
               institutional guidelines)&#xD;
  &#xD;
            -  STEP 1: Leukocytes &gt;= 2 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 1: Absolute neutrophil count &gt;= 1.0 x 10^3/uL (within 28 days prior to&#xD;
               registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional&#xD;
               guidelines)&#xD;
  &#xD;
            -  STEP 1: Platelets &gt;= 50 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 1: Total bilirubin =&lt; 1.5 times the institutional upper limit of normal (ULN)&#xD;
               unless history of Gilbert's disease. Participants with history of Gilbert's disease&#xD;
               must have total bilirubin =&lt; 5 x institutional ULN (within 28 days prior to&#xD;
               registration)&#xD;
  &#xD;
            -  STEP 1: Direct bilirubin =&lt; 2.0 mg/dL (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 1: Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =&lt; 3x upper&#xD;
               limit of normal (ULN) (except if secondary to hepatic involvement) (within 28 days&#xD;
               prior to registration)&#xD;
  &#xD;
            -  STEP 1: Alkaline phosphatase =&lt; 750 U/L (except if secondary to hepatic involvement)&#xD;
               (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 1: Participants must have a serum creatinine =&lt; the institutional (I)ULN OR&#xD;
               measured OR calculated creatinine clearance &gt;= 30 mL/min using the following&#xD;
               Cockcroft-Gault formula. This specimen must have been drawn and processed within 28&#xD;
               days prior to registration&#xD;
  &#xD;
            -  STEP 1: If peripheral neuropathy is present at diagnosis, participants must be grade 2&#xD;
               (moderate symptoms; limiting instrumental activity of daily living [ADL]) or less&#xD;
  &#xD;
            -  STEP 1: Participants must have adequate cardiac function. Participants with known&#xD;
               history or current symptoms of cardiac disease, or history of treatment with&#xD;
               cardiotoxic agents, must have a clinical risk assessment of cardiac function using the&#xD;
               New York Heart Association Functional Classification. To be eligible for this trial,&#xD;
               participants must be class 2 or better&#xD;
  &#xD;
            -  STEP 1: Participants must not be seropositive for hepatitis B (defined by a positive&#xD;
               test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e.,&#xD;
               subjects who are HBsAg negative but positive for antibodies to hepatitis B core&#xD;
               antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must&#xD;
               be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B&#xD;
               virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be&#xD;
               excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination&#xD;
               (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV&#xD;
               vaccination, do not need to be tested for HBV DNA by PCR&#xD;
  &#xD;
            -  STEP 1: Participants with a history of hepatitis C virus (HCV) infection must have&#xD;
               been treated and cured. Participants currently being treated for HCV infection must&#xD;
               have undetectable HCV viral load test on the most recent test results obtained within&#xD;
               6 months prior to registration, if indicated&#xD;
  &#xD;
            -  STEP 1: Participants must not have concurrent multiple myeloma as defined by the&#xD;
               presence of lytic bone disease, plasmacytomas, &gt;= 60% plasma cells in the bone marrow,&#xD;
               or hypercalcemia. Participants will not be excluded solely based on the presence of&#xD;
               plasma cells &gt; 10% in the bone marrow unless the plasma cell percentage exceeds &gt;60%&#xD;
  &#xD;
            -  STEP 1: Participants must not have known allergies to any of the study drugs&#xD;
  &#xD;
            -  STEP 1: Participants must not have had a major surgery within 14 days prior to&#xD;
               registration and be fully recovered from surgery completed within 14 days prior to&#xD;
               registration&#xD;
  &#xD;
            -  STEP 1: Participants must not have a known chronic obstructive pulmonary disease with&#xD;
               a forced expiratory volume in 1 second (FEV1) &lt; 50% of predicted normal&#xD;
  &#xD;
            -  STEP 1: Participants with known human immunodeficiency virus (HIV)-infection must be&#xD;
               on effective anti-retroviral therapy at registration and have undetectable viral load&#xD;
               test on the most recent test results obtained within 6 months prior to registration&#xD;
  &#xD;
            -  STEP 1: Participants must not have either moderate or severe persistent asthma within&#xD;
               the past 2 years), or currently have uncontrolled asthma of any classification. (Note&#xD;
               that subjects who currently have controlled intermittent asthma or controlled mild&#xD;
               persistent asthma are allowed in the study)&#xD;
  &#xD;
            -  STEP 1: Participants must not have uncontrolled diabetes within 28 days prior to&#xD;
               registration&#xD;
  &#xD;
            -  STEP 1: Participants must not have uncontrolled blood pressure and hypertension within&#xD;
               14 days prior to registration. Participants must have a supine systolic BP of &gt;= 90&#xD;
               mmHg&#xD;
  &#xD;
            -  STEP 1: Participants must not have a prior or concurrent malignancy whose natural&#xD;
               history or treatment (in the opinion of the treating physician) has the potential to&#xD;
               interfere with the safety or efficacy assessment of the investigational regimen&#xD;
  &#xD;
            -  STEP 1: Participants must not have received vaccination with live attenuated vaccines&#xD;
               within 28 days prior to Registration to Step 1&#xD;
  &#xD;
            -  STEP 1: Participants must not have uncontrolled infection at the discretion of the&#xD;
               enrolling physician and to be discussed with the study chair if the participant is on&#xD;
               active anti-infectious therapy. Any patient on active anti-microbial therapy for&#xD;
               chronic infectious issues should be discussed with the study chair prior to enrollment&#xD;
  &#xD;
            -  STEP 1: Participants must not be pregnant or nursing (nursing includes breast milk fed&#xD;
               to an infant by any means, including from the breast, milk expressed by hand, or&#xD;
               pumped). Individuals who are of reproductive potential must have agreed to use an&#xD;
               effective contraceptive method with details provided as a part of the consent process.&#xD;
               A person who has had menses at any time in the preceding 12 consecutive months or who&#xD;
               has semen likely to contain sperm is considered to be of &quot;reproductive potential.&quot; In&#xD;
               addition to routine contraceptive methods, &quot;effective contraception&quot; also includes&#xD;
               refraining from sexual activity that might result in pregnancy and surgery intended to&#xD;
               prevent pregnancy (or with a side-effect of pregnancy prevention) including&#xD;
               hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and&#xD;
               vasectomy with testing showing no sperm in the semen&#xD;
  &#xD;
            -  STEP 1: Participants must be offered the opportunity to participate in specimen&#xD;
               banking. With participant consent, specimens must be collected and submitted via the&#xD;
               Southwestern Oncology group (SWOG) Specimen Tracking System&#xD;
  &#xD;
            -  STEP 1: Participants must agree to have blood, bone marrow core biopsy and aspirate,&#xD;
               and fat pad biopsy specimens submitted for minimal residual disease assessment and&#xD;
               future exploratory studies&#xD;
  &#xD;
            -  STEP 1: Participants who can complete PRO, QOL, PRO-CTCAE questionnaires, etc. forms&#xD;
               in English, Spanish and French must participate in the patient-reported outcomes and&#xD;
               quality of life&#xD;
  &#xD;
            -  STEP 2: Participants must have met all eligibility criteria for Step-1 registration&#xD;
  &#xD;
            -  STEP 2: Participants must have achieved at least a partial response&#xD;
  &#xD;
            -  STEP 2: Participants must continue receiving at least one of study drugs (bortezomib,&#xD;
               cyclophosphamide, or daratumumab and hyaluronidase-fihj) if another study drug&#xD;
               (daratumumab and hyaluronidase-fihj, cyclophosphamide, or bortezomib) has been&#xD;
               discontinued due to adverse events. Note: daratumumab and hyaluronidase-fihj cannot be&#xD;
               permanently discontinued&#xD;
  &#xD;
            -  STEP 2: Participants must have completed induction therapy&#xD;
  &#xD;
            -  STEP 2: Participants must be registered to Step 2 within 42 days of cycle 3, day 28 of&#xD;
               induction therapy&#xD;
  &#xD;
            -  STEP 2: Participants must plan to initiate their assigned consolidation therapy within&#xD;
               8 weeks after randomization&#xD;
  &#xD;
            -  STEP 2: Participants must not have experienced a MOD-PFS event&#xD;
  &#xD;
            -  STEP 2: Participants must have ECOG performance score (PS) of 0, 1, or 2 (PS = 3 may&#xD;
               be allowed if secondary to neuropathy)&#xD;
  &#xD;
            -  STEP 2: Participant must have a complete medical history and physical exam within 28&#xD;
               days prior to registration&#xD;
  &#xD;
            -  STEP 2: Participants must be willing to undergo high dose chemotherapy and autologous&#xD;
               stem cell transplantation if they are randomized to the arm receiving high dose&#xD;
               chemotherapy and autologous stem cell transplantation&#xD;
  &#xD;
            -  STEP 2: Participants randomized to Arm 2 must be willing and able to return to a&#xD;
               participating treatment center for their assigned treatment after transplant. Note&#xD;
               that participants need not to have a direct relationship with the transplant center in&#xD;
               order to register&#xD;
  &#xD;
            -  STEP 2: Participants must be eligible to receive high dose chemotherapy with melphalan&#xD;
               at a dose of 200 mg/m^2 or 140 mg/m^2 (200 mg/m^2 is highly encouraged but not&#xD;
               mandated). Transplant eligibility criteria are included in the general eligibility&#xD;
               criteria listed below:&#xD;
  &#xD;
                 -  Patient must have a supine systolic BP &gt;= 90 mmHg (at registration step-1, this&#xD;
                    may not by supported by midodrine)&#xD;
  &#xD;
                 -  Patient must have non-severe cardiac AL as defined by:&#xD;
  &#xD;
                      -  NT proBNP &lt;5000 (if no NTproBNP, BNP must be available and &lt; 400 pg/mL)&#xD;
                         (within 14 days prior to registration step-2)&#xD;
  &#xD;
                      -  TnT &lt; 0.06. If not available, one of the following two criteria must be met&#xD;
                         (within 14 days prior to registration step-2)&#xD;
  &#xD;
                           -  hsTnT &lt;75 or troponin I &lt; 0.1ng/dL&#xD;
  &#xD;
                      -  NYHA I or II (within 14 days prior to registration step-2)&#xD;
  &#xD;
                      -  Cardiac EF &gt;= 40% (within 14 days prior to registration step-2)&#xD;
  &#xD;
            -  STEP 2: Hemoglobin &gt; 8.0 g/dL (&gt; 5 mmol/L); red blood cell transfusion allowed up to 7&#xD;
               days prior to registration (within 28 days prior to registration) (NOTE: Growth factor&#xD;
               support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 2: Leukocytes &gt;= 2 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 2: Absolute neutrophil count &gt;= 1.0 x 10^3/uL (within 28 days prior to&#xD;
               registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional&#xD;
               guidelines)&#xD;
  &#xD;
            -  STEP 2: Platelets &gt;= 50 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 2: Total bilirubin =&lt; 1.5 times the institutional ULN unless history of Gilbert's&#xD;
               disease. Participants with history of Gilbert's disease must have total bilirubin =&lt; 5&#xD;
               x institutional ULN (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 2: Direct bilirubin =&lt; 2.0 mg/dL (except if secondary to hepatic involvement)&#xD;
               (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 2: AST/ALT =&lt; 3x upper limit of normal (ULN) (except if secondary to hepatic&#xD;
               involvement) (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 2: Alkaline phosphatase =&lt; 750 U/L (except if secondary to hepatic involvement)&#xD;
               (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 2: Participants must have a serum creatinine =&lt; the IULN OR calculated creatinine&#xD;
               clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must&#xD;
               have been drawn and processed within 28 days prior to registration&#xD;
  &#xD;
            -  STEP 2: Participants must not have uncontrolled infection at the discretion of the&#xD;
               enrolling physician and to be discussed with the study chair if the participant is on&#xD;
               active anti-infectious therapy. Any patient on active anti-microbial therapy for&#xD;
               chronic infectious issues should be discussed with the study chair prior to enrollment&#xD;
  &#xD;
            -  STEP 2: Participants randomized to the ASCT arm must be able to have at least 2.0 x&#xD;
               10^6 CD34 cells/kg collected&#xD;
  &#xD;
            -  STEP 2: Participants who can complete PRO, QOL, PRO-CTCAE questionnaires, etc. forms&#xD;
               in English, Spanish and French must participate in the patient-reported outcomes and&#xD;
               quality of life&#xD;
  &#xD;
            -  STEP 3: Participants must have met all eligibility criteria for Step-1 and Step-2&#xD;
               registration&#xD;
  &#xD;
            -  STEP 3: Participants must not have had daratumumab and hyaluronidase-fihj permanently&#xD;
               discontinued during induction or consolidation&#xD;
  &#xD;
            -  STEP 3: Participants must have completed induction and consolidation therapy&#xD;
  &#xD;
            -  STEP 3: Participants must be registered to Step 3 within the following time frames:&#xD;
  &#xD;
                 -  If randomized to Arm 1 Dara-VCD consolidation: within 28 days of completion of 3&#xD;
                    cycles of consolidation therapy&#xD;
  &#xD;
                 -  If randomized to Arm 2 high dose chemotherapy and autologous stem cell&#xD;
                    transplantation: within 180 days following initiation of stem cell&#xD;
                    transplantation&#xD;
  &#xD;
            -  STEP 3: Participants must not have experienced a MOD-PFS event&#xD;
  &#xD;
            -  STEP 3: Participants must have ECOG performance score (PS) of 0, 1, or 2 (PS = 3 is&#xD;
               allowed if secondary to neuropathy)&#xD;
  &#xD;
            -  STEP 3: Participants must have a complete medical history and physical exam within 28&#xD;
               DAYS prior to registration&#xD;
  &#xD;
            -  STEP 3: Hemoglobin &gt; 8.0 g/dL (&gt; 5 mmol/L); red blood cell transfusion allowed up to 7&#xD;
               days prior to registration (within 28 days prior to registration) (NOTE: Growth factor&#xD;
               support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 3: Leukocytes &gt;= 2 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 3: Absolute neutrophil count &gt;= 1.0 x 10^3/uL (within 28 days prior to&#xD;
               registration) (NOTE: Growth factor support [G-CSF] is permitted per institutional&#xD;
               guidelines)&#xD;
  &#xD;
            -  STEP 3: Platelets &gt;= 50 x 10^3/uL (within 28 days prior to registration) (NOTE: Growth&#xD;
               factor support [G-CSF] is permitted per institutional guidelines)&#xD;
  &#xD;
            -  STEP 3: Total bilirubin =&lt; 1.5 times the institutional upper limit of normal (ULN)&#xD;
               unless history of Gilbert's disease. Participants with history of Gilbert's disease&#xD;
               must have total bilirubin =&lt; 5 x institutional ULN (within 28 days prior to&#xD;
               registration)&#xD;
  &#xD;
            -  STEP 3: Direct bilirubin =&lt; 2.0 mg/dL (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 3: AST/ALT =&lt; 3x upper limit of normal (ULN) (except if secondary to hepatic&#xD;
               involvement) (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 3: Alkaline phosphatase =&lt; 750 U/L (except if secondary to hepatic involvement)&#xD;
               (within 28 days prior to registration)&#xD;
  &#xD;
            -  STEP 3: Participants must not have uncontrolled infection at the discretion of the&#xD;
               enrolling physician and to be discussed with the study chair if the participant is on&#xD;
               active anti-infectious therapy. Any patient on active anti-microbial therapy for&#xD;
               chronic infectious issues should be discussed with the study chair prior to enrollment&#xD;
  &#xD;
            -  Participants must be informed of the investigational nature of this study and must&#xD;
               sign and give informed consent in accordance with institutional and federal&#xD;
               guidelines.&#xD;
  &#xD;
          For participants with impaired decision-making capabilities, legally authorized&#xD;
          representatives may sign and give informed consent on behalf of study participants in&#xD;
          accordance with applicable federal, local, and Central Institutional Review Board (CIRB)&#xD;
          regulations&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Patrick A Hagen</last_name>
      <role>Principal Investigator</role>
      <affiliation>SWOG Cancer Research Network</affiliation>
    </overall_official>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Immunoglobulin Light-chain Amyloidosis</mesh_term>
      <mesh_term>Amyloidosis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dexamethasone</mesh_term>
      <mesh_term>Dexamethasone acetate</mesh_term>
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Melphalan</mesh_term>
      <mesh_term>Mechlorethamine</mesh_term>
      <mesh_term>Nitrogen Mustard Compounds</mesh_term>
      <mesh_term>Bortezomib</mesh_term>
      <mesh_term>Daratumumab</mesh_term>
      <mesh_term>Antibodies, Monoclonal</mesh_term>
      <mesh_term>BB 1101</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06022939
  org study id: S2213
  secondary id: NCI-2023-04234
  secondary id: S2213
  secondary id: S2213
  secondary id: U10CA180888
  nct id: NCT06022939
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase III trial compares the effect of adding a stem cell transplant with melphalan
        after completing chemotherapy with daratumumab, cyclophosphamide, bortezomib and
        dexamethasone (Dara-VCD) versus chemotherapy with Dara-VCD alone for treating patients with
        newly diagnosed amyloid light chain (AL) amyloidosis. Melphalan is a chemotherapy given prior
        to a stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant
        helps kill cancer cells in the body and helps make room in the patient's bone marrow for new
        blood-forming cells (stem cells) to grow. The stem cells are then returned to the patients to
        replace the blood forming cells that were destroyed by the chemotherapy. Daratumumab is in a
        class of medications called monoclonal antibodies. It binds to a protein called CD38, which
        is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab
        may block CD38 and help the immune system kill cancer cells. Chemotherapy drugs, such as
        cyclophosphamide and bortezomib, work in different ways to stop the growth of cancer cells,
        either by killing the cells, by stopping them from dividing, or by stopping them from
        spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to
        lower the body's immune response to help stop the growth of cancer cells. Giving a stem cell
        transplant with melphalan after Dara-VCD may kill more cancer cells in patients with newly
        diagnosed AL amyloidosis.
  PRIMARY OBJECTIVE:
  
        I. To compare major organ deterioration progression-free survival between participants
        randomized to the autologous stem cell transplant (ASCT) and non-ASCT arms of this study.
  
        SECONDARY OBJECTIVES:
  
        I. To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT
        arms of this study.
  
        II. To compare rates of cardiac and renal organ responses between participants randomized to
        the ASCT and non-ASCT arms of this study.
  
        III. To compare rates of cardiac and renal organ progression between participants randomized
        to the ASCT and non-ASCT arms of the study.
  
        IV. To compare the frequency and severity of toxicities between participants randomized to
        the ASCT and non-ASCT arms of this study.
  
        V. To compare minimal residual disease (MRD) negativity rates between participants randomized
        to the ASCT and non-ACST arms of this study.
  
        ADDITIONAL OBJECTIVES:
  
        I. To compare the best overall hematologic response rates between participants randomized to
        the ASCT and non-ASCT arms of this study.
  
        II. To compare rates of hematologic complete response (CR) and very good partial response,
        following completion of consolidation therapy between participants randomized to the ASCT and
        non-ASCT arms of this study, post-consolidation.
  
        III. To compare hematologic progression-free survival between participants randomized to the
        ASCT and non-ASCT arms of this study.
  
        IV. To compare time to next treatment between participants randomized to the ASCT and
        non-ASCT arms of the study.
  
        V. To evaluate utilization of delayed ASCT in participants randomized to the non-ASCT arm of
        the study.
  
        TRANSLATIONAL MEDICINE PRIMARY OBJECTIVES:
  
        I. To compare MRD negativity rates from bone marrow aspirates via next generation flow
        cytometry (NGF) between the ASCT and non-ASCT arms of this study post-consolidation.
  
        II. To bank specimens for future use.
  
        TRANSLATIONAL MEDICINE EXPLORATORY OBJECTIVES:
  
        I. To evaluate MRD negativity rates at post-induction, and compare MRD negativity rates at 12
        months post-consolidation from bone marrow aspirates via NGF between participants randomized
        to the ASCT and non-ASCT arms of this study.
  
        II. To investigate the association of achieving MRD negativity at any point (post-induction,
        post-consolidation, or 12 months post-consolidation) via NGF from bone marrow aspirates with
        major organ deterioration-progression free survival (MOD-PFS).
  
        III. To investigate the association of achieving sustained MRD negativity (MRD negative at
        two consecutive measurements -- post-induction, post-consolidation, and 12 months
        post-consolidation) via NGF from bone marrow aspirates with MOD-PFS.
  
        QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE:
  
        I. To compare patient-reported physical function following consolidation treatment between
        participants randomized to the ASCT and non-ASCT arms using the Patient Reported Outcomes
        Measurement Information System (PROMIS)-29+2 Profile version (v) 2.1 physical function
        sub-scale.
  
        QOL SECONDARY OBJECTIVES:
  
        I. To compare patient-reported fatigue following consolidation treatment between participants
        randomized to the ASCT and non-ASCT arms using the PROMIS-29 fatigue subscale.
  
        II. To compare longitudinal changes in physical function using the PROMS-29+2 between
        participants randomized to the ASCT and non-ASCT arms.
  
        QOL EXPLORATORY OBJECTIVES:
  
        I. To assess baseline symptom burden in AL amyloidosis patients prior to induction therapy
        using the PROMIS-29+2.
  
        II. To compare mean scores of symptom scales using the PROMIS-29+2 following consolidation
        treatment, and at 6 months and 12 months from step 3 registration between treatment arms.
  
        III. To compare mean scores of functional scales using the PROMIS-29+2, following
        consolidation treatment, and at 6 months and 12 months from step 3 registration between
        treatment arms.
  
        IV. To explore whether longitudinal changes in symptoms, functioning, and overall heath
        related quality of life (HRQoL) as assessed by the PROMIS-29 +2 (version 2.1) differ
        according to treatment group and, separately, according to baseline cardiac or renal
        involvement using interaction tests between participants randomized to the ASCT and non-ASCT
        arms.
  
        V. To compare health utility indices using the PROMIS preference score (PROPr) between
        patients randomized to the ASCT and non-ASCT arms.
  
        PATIENT REPORTED OUTCOME (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) PRIMARY
        OBJECTIVE:
  
        I. To compare patient reported symptoms regarding treatment emergent adverse events of
        interest using the Patient Reported Outcome CTCAE (PRO-CTCAE) Measurement System between
        patients randomized to the ASCT and non-ASCT arms of this study.
  
        OUTLINE:
  
        INDUCTION: Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) over 3-5
        minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients
        receive bortezomib SC over 3-5 minutes, cyclophosphamide orally (PO) or intravenously (IV),
        and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days
        for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients
        undergo computed tomography (CT), magnetic resonance imaging (MRI) or positron emission
        tomography (PET)-CT and fat pad aspiration at screening. Patients undergo echocardiography at
        screening, the completion of induction, and at progression. Patients undergo bone marrow
        aspiration and biopsy at screening, post induction treatment and at progression. Patients
        undergo blood and urine sample collection at screening, at the start of each cycle, and the
        end of treatment and during follow up or at progression.
  
        CONSOLIDATION: Patients who achieve an overall response of partial response or better after 3
        cycles of Dara-VCD are randomized to 1 of 2 arms.
  
        ARM I: Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and
        15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO
        or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles
        in the absence of disease progression or unacceptable toxicity. Patients undergo
        echocardiography at screening and at progression. Patients undergo bone marrow aspiration and
        biopsy within14-28 days post consolidation treatment and at progression. Patients undergo
        blood and urine sample collection at screening, at the start of each cycle, and the end of
        treatment and during follow up or at progression.
  
        ARM II: Patients undergo collection of peripheral blood stem cells. Patients receive
        melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the
        absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at
        screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90
        days post initiation of stem cell transplant. Patients undergo blood and urine sample
        collection at screening, during treatment, and the end of treatment and during follow up or
        at progression.
  
        MAINTENANCE: Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5
        minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence
        of disease progression or unacceptable toxicity. Patients undergo echocardiography at
        screening, 12 months post consolidation treatment and at progression. Patients undergo bone
        marrow aspiration and biopsy 12 months post consolidation treatment and at progression.
        Patients undergo blood and urine sample collection at screening, during treatment, 12 months
        post consolidation treatment and during follow up or at progression.
  
        After completion of study treatment, patients are followed up every 3 or 6 months up to 4
        years after registration.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Major organ deterioration progression-free survival (PFS)
  time frame: From date of randomization (Step 2 registration) to date of first documentation of hematologic progression, cardiac organ progression, renal organ progression, or death due to any cause, assessed up to 4 years
  description: Will be performed using a stratified log-rank test for comparison between study arms. The analyses will be stratified according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 versus [vs.] 2-3), hematological response following 2 cycles of daratumumab, cyclophosphamide, bortezomib and dexamethasone (Dara-VCD) induction (partial response [PR] or worse vs. very good partial response [VGPR] or better), and presence of t(11;14) by interphase fluorescence in situ hybridization [iFISH] (yes vs. no). All eligible participants will be considered in analyses of the primary endpoint, according to their assigned arm at randomization.
  measure: Overall survival
  time frame: From randomization to date of death due to any cause, assessed up to 4 years
  description: Will be performed using a stratified log-rank test for comparison between arms, with stratification according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. [VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Hematologic PFS
  time frame: From randomization (Step 2 registration) to date of first documentation of hematologic progression, or death due to any cause, assessed up to 4 years
  description: Will be performed using a stratified log-rank test for comparison between arms, with stratification according to Mayo 2012 Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Cardiac and renal organ response rates
  time frame: Up to 4 years
  description: Progression will be defined based on objective evidence of worsening of organ dysfunction due to AL amyloid. Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Measurable residual disease (MRD) negativity rate
  time frame: From baseline to off treatment follow-up (prior to progression) or 12 months post consolidation
  description: Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Best overall hematologic response
  time frame: From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years
  description: Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Overall hematologic response rate
  time frame: From date of initial registration (Step 1) and date of randomization (Step 2 registration) to date of first documentation of hematologic PR, VGPR, or CR, assessed up to 4 years
  description: Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Rate of complete response
  time frame: Up to 4 years
  description: Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Rate of very good complete response or better
  time frame: Up to 4 years
  description: Will be evaluated with a Cochran-Mantel-Haenszel test accounting for stratification according to Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Time to next treatment
  time frame: From date of initial registration (Step 1) to date of initiation of next line of therapy, assessed up to 4 years
  description: Will be analyzed using the cumulative incidence competing risks method.
  measure: Change in patient reported health quality of life (QOL)
  time frame: From baseline to post-maintenance, approximately 24 months
  description: Will use the PROMIS-29+2 (version 2.1) to compare the physical function between participants in the ASCT vs. non-ASCT arm.
  measure: Incidence of adverse events
  time frame: Up to the end of maintenance therapy, approximately 24 months
  description: Participant-reported toxicity will be examined using Patient Reported Outcome-Common Terminology Criteria for Adverse Events.
  measure: Bone marrow Next Generation Flow based MRD negativity rates
  time frame: At the end of consolidation, approximately 6 months
  description: Comparisons of MRD negativity rates between arms will be made using a stratified Cochran-Mantel-Haenszel test, with analyses stratified according to European modification of the Mayo Prognostic Staging System for Light Chain Amyloidosis (Stage 1 vs. 2-3a), hematological response following 2 cycles of Dara-VCD induction (PR or worse vs. VGPR or better), and presence of t(11;14) by iFISH (yes vs. no).
  measure: Change in physical function as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS)-29+2 physical function domain
  time frame: From baseline to post-consolidation, approximately 6 months
  description: Analysis will be conducted using multiple linear regression analysis, adjusting for the clinical study-specified stratification factors (which are also anticipated to influence QOL endpoints), and the baseline score as covariates.
  measure: Change in PROMIS-29 fatigue domain score
  time frame: From baseline to post-consolidation, approximately 6 months
  description: Analysis will be conducted using linear regression, adjusting for the clinical study-specified stratification factors and the baseline PROMIS-29 fatigue domain score as covariates. Additionally, will conduct longitudinal modeling of the physical function domain score over time (through 12 months from registration Step 3). For longitudinal modeling, linear mixed models will be used.
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group type: Active Comparator
  description: Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1 and 15 as well as bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within14-28 days post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  arm group type: Experimental
  description: Patients undergo collection of peripheral blood stem cells. Patients receive melphalan IV for 1 cycle and then 2 days later receive the stem cell transplant IV in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening and at progression. Patients undergo bone marrow aspiration and biopsy within 60-90 days post initiation of stem cell transplant. Patients undergo blood and urine sample collection at screening, during treatment, and the end of treatment and during follow up or at progression.
  arm group label: Induction (Chemotherapy)
  arm group type: Experimental
  description: Patients receive daratumumab and hyaluronidase-fihj SC over 3-5 minutes on days 1, 8, 15 and 22 for 2 cycles and then days 1 and 15 for cycle 3. Patients receive bortezomib SC over 3-5 minutes, cyclophosphamide PO or IV, and dexamethasone PO or IV on days 1, 8, 15 and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI or PET-CT and fat pad aspiration at screening. Patients undergo echocardiography at screening, the completion of induction, and at progression. Patients undergo bone marrow aspiration and biopsy at screening, post induction treatment and at progression. Patients undergo blood and urine sample collection at screening, at the start of each cycle, and the end of treatment and during follow up or at progression.
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  arm group type: Experimental
  description: Patients receive maintenance daratumumab and hyaluronidase-fihj SC over 3-5 minutes on day 1 of each cycle. Cycles repeat every 28 days for up 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography at screening, 12 months post consolidation treatment and at progression. Patients undergo bone marrow aspiration and biopsy 12 months post consolidation treatment and at progression. Patients undergo blood and urine sample collection at screening, during treatment, 12 months post consolidation treatment and during follow up or at progression.
  intervention type: Procedure
  intervention name: Autologous Hematopoietic Stem Cell Transplantation
  description: Given IV
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  other name: AHSCT
  other name: Autologous
  other name: Autologous Hematopoietic Cell Transplantation
  other name: Autologous Stem Cell Transplant
  other name: Autologous Stem Cell Transplantation
  other name: Stem Cell Transplantation, Autologous
  intervention type: Procedure
  intervention name: Biopsy
  description: Undergo fat pad biopsy
  arm group label: Induction (Chemotherapy)
  other name: BIOPSY_TYPE
  other name: Bx
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood and urine specimen collection
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  arm group label: Induction (Chemotherapy)
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Bone Marrow Aspiration
  description: Undergo bone marrow aspiration
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  arm group label: Induction (Chemotherapy)
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  intervention type: Procedure
  intervention name: Bone Marrow Biopsy
  description: Undergo bone marrow biopsy
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  arm group label: Induction (Chemotherapy)
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  other name: Biopsy of Bone Marrow
  other name: Biopsy, Bone Marrow
  intervention type: Drug
  intervention name: Bortezomib
  description: Given SC
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Induction (Chemotherapy)
  other name: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  other name: LDP 341
  other name: MLN341
  other name: PS-341
  other name: PS341
  other name: Velcade
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT scan
  arm group label: Induction (Chemotherapy)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: Given PO or IV
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Induction (Chemotherapy)
  other name: (-)-Cyclophosphamide
  other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  other name: Carloxan
  other name: Ciclofosfamida
  other name: Ciclofosfamide
  other name: Cicloxal
  other name: Clafen
  other name: Claphene
  other name: CP monohydrate
  other name: CTX
  other name: CYCLO-cell
  other name: Cycloblastin
  other name: Cycloblastine
  other name: Cyclophospham
  other name: Cyclophosphamid monohydrate
  other name: Cyclophosphamide Monohydrate
  other name: Cyclophosphamidum
  other name: Cyclophosphan
  other name: Cyclophosphane
  other name: Cyclophosphanum
  other name: Cyclostin
  other name: Cyclostine
  other name: Cytophosphan
  other name: Cytophosphane
  other name: Cytoxan
  other name: Fosfaseron
  other name: Genoxal
  other name: Genuxal
  other name: Ledoxina
  other name: Mitoxan
  other name: Neosar
  other name: Revimmune
  other name: Syklofosfamid
  other name: WR- 138719
  intervention type: Drug
  intervention name: Daratumumab and Hyaluronidase-fihj
  description: Given SC
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Induction (Chemotherapy)
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  other name: DARA Co-formulated with rHuPH20
  other name: DARA/rHuPH20
  other name: Daratumumab + rHuPH20
  other name: Daratumumab with rHuPH20
  other name: Daratumumab-rHuPH20
  other name: Daratumumab/Hyaluronidase-fihj
  other name: Daratumumab/rHuPH20 Co-formulation
  other name: Darzalex Faspro
  other name: Darzalex/rHuPH20
  other name: HuMax-CD38-rHuPH20
  other name: Recombinant Human Hyaluronidase Mixed with Daratumumab
  intervention type: Drug
  intervention name: Dexamethasone
  description: Given PO or IV
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Induction (Chemotherapy)
  other name: Aacidexam
  other name: Adexone
  other name: Aknichthol Dexa
  other name: Alba-Dex
  other name: Alin
  other name: Alin Depot
  other name: Alin Oftalmico
  other name: Amplidermis
  other name: Anemul mono
  other name: Auricularum
  other name: Auxiloson
  other name: Baycadron
  other name: Baycuten
  other name: Baycuten N
  other name: Cortidexason
  other name: Cortisumman
  other name: Decacort
  other name: Decadrol
  other name: Decadron
  other name: Decadron DP
  other name: Decalix
  other name: Decameth
  other name: Decasone R.p.
  other name: Dectancyl
  other name: Dekacort
  other name: Deltafluorene
  other name: Deronil
  other name: Desamethasone
  other name: Desameton
  other name: Dexa-Mamallet
  other name: Dexa-Rhinosan
  other name: Dexa-Scheroson
  other name: Dexa-sine
  other name: Dexacortal
  other name: Dexacortin
  other name: Dexafarma
  other name: Dexafluorene
  other name: Dexalocal
  other name: Dexamecortin
  other name: Dexameth
  other name: Dexamethasone Intensol
  other name: Dexamethasonum
  other name: Dexamonozon
  other name: Dexapos
  other name: Dexinoral
  other name: Dexone
  other name: Dinormon
  other name: Dxevo
  other name: Fluorodelta
  other name: Fortecortin
  other name: Gammacorten
  other name: Hemady
  other name: Hexadecadrol
  other name: Hexadrol
  other name: Lokalison-F
  other name: Loverine
  other name: Methylfluorprednisolone
  other name: Millicorten
  other name: Mymethasone
  other name: Orgadrone
  other name: Spersadex
  other name: TaperDex
  other name: Visumetazone
  other name: ZoDex
  intervention type: Procedure
  intervention name: Echocardiography
  description: Undergo echocardiography
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  arm group label: Induction (Chemotherapy)
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  other name: EC
  intervention type: Procedure
  intervention name: Magnetic Resonance Imaging
  description: Undergo MRI
  arm group label: Induction (Chemotherapy)
  other name: Magnetic Resonance
  other name: Magnetic resonance imaging (procedure)
  other name: Magnetic Resonance Imaging Scan
  other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  other name: MR
  other name: MR Imaging
  other name: MRI
  other name: MRI Scan
  other name: NMR Imaging
  other name: NMRI
  other name: Nuclear Magnetic Resonance Imaging
  intervention type: Drug
  intervention name: Melphalan
  description: Given IV
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  other name: Alanine Nitrogen Mustard
  other name: CB-3025
  other name: L-PAM
  other name: L-Phenylalanine Mustard
  other name: L-Sarcolysin
  other name: L-Sarcolysin Phenylalanine mustard
  other name: L-Sarcolysine
  other name: Melphalanum
  other name: Phenylalanine Mustard
  other name: Phenylalanine Nitrogen Mustard
  other name: Sarcoclorin
  other name: Sarkolysin
  other name: WR-19813
  intervention type: Procedure
  intervention name: Positron Emission Tomography
  description: Undergo PET-CT
  arm group label: Induction (Chemotherapy)
  other name: Medical Imaging, Positron Emission Tomography
  other name: PET
  other name: PET Scan
  other name: Positron emission tomography (procedure)
  other name: Positron Emission Tomography Scan
  other name: Positron-Emission Tomography
  other name: proton magnetic resonance spectroscopic imaging
  other name: PT
  intervention type: Procedure
  intervention name: Stem Cell Isolation
  description: Undergo stem cell collection
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  other name: Isolation, Stem Cell
  other name: Stem Cell Collection
  other name: Stem Cell Recovery
  intervention type: Other
  intervention name: Survey Administration
  description: Ancillary study
  arm group label: Consolidation Arm I (Chemotherapy)
  arm group label: Consolidation Arm II (Chemotherapy, ASCT)
  arm group label: Induction (Chemotherapy)
  arm group label: Maintenance (daratumumab and hyaluronidase-fihj)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Patrick A Hagen
  role: Principal Investigator
  affiliation: SWOG Cancer Research Network
  responsible party type: Sponsor
  mesh term: Immunoglobulin Light-chain Amyloidosis
  mesh term: Amyloidosis
  mesh term: Dexamethasone
  mesh term: Dexamethasone acetate
  mesh term: Cyclophosphamide
  mesh term: Melphalan
  mesh term: Mechlorethamine
  mesh term: Nitrogen Mustard Compounds
  mesh term: Bortezomib
  mesh term: Daratumumab
  mesh term: Antibodies, Monoclonal
  mesh term: BB 1101