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/NCT06042725</url>
    </required_header>
    <id_info>
      <org_study_id>MC210808</org_study_id>
      <secondary_id>NCI-2023-06776</secondary_id>
      <secondary_id>MC210808</secondary_id>
      <secondary_id>22-009930</secondary_id>
      <nct_id>NCT06042725</nct_id>
    </id_info>
    <brief_title>Venetoclax in Combination With Lenalidomide and Dexamethasone (Ven-Rd), Daratumumab and Dexamethasone (Ven-Dd), or Daratumumab-Lenalidomide-Dexamethasone (Ven-DRd) for the Treatment of Multiple Myeloma</brief_title>
    <official_title>Phase I Clinical Trial of Bcl2 Inhibitor Venetoclax in Combination With Lenalidomide and Dexamethasone (Ven-Rd), Daratumumab and Dexamethasone (Ven-Dd), or Daratumumab-Lenalidomide-Dexamethasone (Ven-DRd) in t(11;14) Multiple Myeloma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Mayo Clinic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Mayo Clinic</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 I trial tests the safety, side effects, and best dose of venetoclax in combination&#xD;
        with lenalidomide and dexamethasone, daratumumab and dexamethasone, or daratumumab,&#xD;
        lenalidomide, and dexamethasone in treating patients with multiple myeloma. Venetoclax is in&#xD;
        a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of&#xD;
        cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Lenalidomide is a&#xD;
        drug that is similar to thalidomide, and is used to treat multiple myeloma and certain types&#xD;
        of anemia. Lenalidomide belongs to the family of drugs called angiogenesis inhibitors.&#xD;
        Dexamethasone is in a class of medications called corticosteroids. It is used to reduce&#xD;
        inflammation and lower the body's immune response to help lessen the side effects of&#xD;
        chemotherapy drugs. Daratumumab is in a class of medications called monoclonal antibodies. It&#xD;
        binds to a protein called CD38, which is found on some types of immune cells and cancer&#xD;
        cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill&#xD;
        cancer cells. Adding venetoclax to the other drug combinations may allow control of the&#xD;
        cancer than is possible with the current treatments.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVE:&#xD;
  &#xD;
        I. To estimate the recommended phase II dose (RP2D) of venetoclax that can be combined with&#xD;
        standard dose daratumumab and dexamethasone (Dd) (Arm A), lenalidomide and dexamethasone (Rd)&#xD;
        (Arm B) or daratumumab, lenalidomide and dexamethasone (DRd) (Arm C) in patients with&#xD;
        t(11;14) multiple myeloma (MM).&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To assess frequency and severity of treatment-emergent adverse events (TEAEs) graded per&#xD;
        National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)&#xD;
        version (v)5.0.&#xD;
  &#xD;
        II. To assess best response while on treatment per International Myeloma Working Group (IMWG)&#xD;
        criteria.&#xD;
  &#xD;
        OUTLINE: This is a dose-escalation study of venetoclax. Patients with relapsed MM (Group 1)&#xD;
        are assigned to Arm B or C. Patients with newly diagnosed MM (Group 2) are assigned to Arm A,&#xD;
        B, or C.&#xD;
  &#xD;
        ARM A: Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle,&#xD;
        daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of&#xD;
        cycles 3-6, and day 1 of cycles 7+, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12.&#xD;
        Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or&#xD;
        unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood&#xD;
        samples during screening. In addition, patients undergo x-rays, whole-body low-dose computed&#xD;
        tomography (WBLDCT), positron emission tomography (PET)/computed tomography (CT) or magnetic&#xD;
        resonance imaging (MRI) scans during screening and on study, and bone marrow aspiration and&#xD;
        biopsy during screening, and during follow-up&#xD;
  &#xD;
        ARM B: Patients receive venetoclax PO QD on days 1-28 of each cycle, lenalidomide PO QD on&#xD;
        days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment&#xD;
        repeats every 28 days for up to 36 cycles in the absence of disease progression or&#xD;
        unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood&#xD;
        samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans&#xD;
        during screening and on study, and bone marrow aspiration and biopsy during screening, and&#xD;
        during follow-up.&#xD;
  &#xD;
        ARM C: Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days&#xD;
        1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+,&#xD;
        lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22&#xD;
        of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease&#xD;
        progression or unacceptable toxicity. Patients also undergo chest x-ray and optional&#xD;
        collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT,&#xD;
        PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy&#xD;
        during screening, on study, and during follow-up.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up at 30 days and then every 3 or&#xD;
        6 months for a total of 3 years.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 28, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2028</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose-limiting toxicity</measure>
      <time_frame>28 Days (1 treatment cycle); Up to 3 years</time_frame>
      <description>Dose-limiting toxicities (DLT) are defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Frequency and severity of treatment-emergent adverse events</measure>
      <time_frame>Up to 30 days after completion of study treatment</time_frame>
      <description>The number and severity of all adverse events (overall and by dose- level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Best response while on treatment</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>The overall response rate and ≥ very good partial response (VGPR) rate will be estimated by the number of patients with each response category (e.g., stringent complete response, complete response, VGPR, partial response, etc) divided by the total number of evaluable patients.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Multiple Myeloma</condition>
    <arm_group>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive venetoclax PO QD on days 1-28 of each cycle, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, on study, and during follow-up.</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo optional collection of blood samples</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</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>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</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>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>Biopsy of Bone Marrow</other_name>
      <other_name>Biopsy, Bone Marrow</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Chest Radiography</intervention_name>
      <description>Undergo chest x-ray</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>Chest X-ray</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo PET/CT</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</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>Biological</intervention_type>
      <intervention_name>Daratumumab</intervention_name>
      <description>Given SC</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>Anti-CD38 Monoclonal Antibody</other_name>
      <other_name>Daratumumab Biosimilar HLX15</other_name>
      <other_name>Daratumumab-fihj</other_name>
      <other_name>Darzalex</other_name>
      <other_name>HLX15</other_name>
      <other_name>HuMax-CD38</other_name>
      <other_name>JNJ-54767414</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dexamethasone</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</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>Drug</intervention_type>
      <intervention_name>Lenalidomide</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>CC-5013</other_name>
      <other_name>CC5013</other_name>
      <other_name>CDC 501</other_name>
      <other_name>Revlimid</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Low Dose Computed Tomography of the Whole Body</intervention_name>
      <description>Undergo WBLDCT</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>Low-dose Whole-body CT</other_name>
      <other_name>Whole Body Low Dose Computed Tomography</other_name>
      <other_name>Whole Body Low Dose CT</other_name>
      <other_name>Whole-body Low-dose CT</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Magnetic Resonance Imaging</intervention_name>
      <description>Undergo MRI</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</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>Procedure</intervention_type>
      <intervention_name>Positron Emission Tomography</intervention_name>
      <description>Undergo PET/CT</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</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>Drug</intervention_type>
      <intervention_name>Venetoclax</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>ABT-0199</other_name>
      <other_name>ABT-199</other_name>
      <other_name>ABT199</other_name>
      <other_name>GDC-0199</other_name>
      <other_name>RG7601</other_name>
      <other_name>Venclexta</other_name>
      <other_name>Venclyxto</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>X-Ray Imaging</intervention_name>
      <description>Undergo x-rays</description>
      <arm_group_label>Arm A (Ven-Dd)</arm_group_label>
      <arm_group_label>Arm B (Ven-Rd)</arm_group_label>
      <arm_group_label>Arm C (Ven-DRd)</arm_group_label>
      <other_name>Conventional X-Ray</other_name>
      <other_name>Diagnostic Radiology</other_name>
      <other_name>Medical Imaging, X-Ray</other_name>
      <other_name>Plain film radiographs</other_name>
      <other_name>Radiographic Imaging</other_name>
      <other_name>Radiographic imaging procedure (procedure)</other_name>
      <other_name>Radiography</other_name>
      <other_name>RG</other_name>
      <other_name>Static X-Ray</other_name>
      <other_name>X-Ray</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosed MM with bone marrow plasma cell fluorescence in situ hybridization (FISH)&#xD;
               test demonstrating presence of t(11;14) at the time of diagnostic bone marrow biopsy&#xD;
               specimen at Mayo Clinic. NOTE: Testing for t(11;14) will be performed using specific&#xD;
               FISH test under an Investigational Device Exemption (IDE). Samples tested beyond 72&#xD;
               hours from the collection will not be considered adequate for trial enrollment&#xD;
  &#xD;
            -  No more than 1 cycle of any commonly used myeloma regimen for treatment of newly&#xD;
               diagnosed MM&#xD;
  &#xD;
            -  No prior treatment for multiple myeloma (group 2) and at least one prior line of&#xD;
               therapy which did not include venetoclax (group 1)&#xD;
  &#xD;
            -  Patient is not being considered for stem cell transplant (group 2, newly diagnosed&#xD;
               only)&#xD;
  &#xD;
            -  Age ≥ 18 years&#xD;
  &#xD;
            -  Calculated creatinine clearance (using Cockcroft-Gault equation) ≥ 30 mL/min (obtained&#xD;
               ≤ 14 days prior to registration)&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) ≥ 1000/uL (without growth factor support) (obtained ≤&#xD;
               14 days prior to registration)&#xD;
  &#xD;
            -  Un-transfused Platelet count ≥ 75000/uL (≥ 50,000/uL if marrow plasma cells [PC]% &gt;&#xD;
               50%) (obtained ≤ 14 days prior to registration)&#xD;
  &#xD;
            -  Hemoglobin ≥ 8.0 g/dL (transfusion permitted) (obtained ≤ 14 days prior to&#xD;
               registration)&#xD;
  &#xD;
            -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (known Gilbert's syndrome are&#xD;
               allowed provided bilirubin ≤ 2.5 mg/dL) (obtained ≤ 14 days prior to registration)&#xD;
  &#xD;
            -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN&#xD;
               (obtained ≤ 14 days prior to registration)&#xD;
  &#xD;
            -  Alkaline phosphatase ≤ 750 U/L (obtained ≤ 14 days prior to registration)&#xD;
  &#xD;
            -  Measurable disease of multiple myeloma as defined by at least ONE of the following:&#xD;
  &#xD;
                 -  Serum monoclonal protein ≥ 1.0 g/dL&#xD;
  &#xD;
                 -  ≥ 200 mg of monoclonal protein in the urine on 24 hour electrophoresis&#xD;
  &#xD;
                 -  Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum&#xD;
                    immunoglobulin kappa to lambda free light chain ratio&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2&#xD;
  &#xD;
            -  Provide written informed consent&#xD;
  &#xD;
            -  Negative serum pregnancy test done ≤ 7 days prior to registration, for women of&#xD;
               childbearing potential only&#xD;
  &#xD;
            -  Willing to follow strict birth control measures as suggested by the study&#xD;
  &#xD;
            -  Female participant is eligible to participate if she is not pregnant or breastfeeding,&#xD;
               and at least one of the following conditions applies:&#xD;
  &#xD;
                 -  Is not a woman of childbearing potential (WOCBP) OR&#xD;
  &#xD;
                 -  Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal&#xD;
                    toxicity and prescribed under a pregnancy prevention/controlled distribution&#xD;
                    program, WOCBP participants will be eligible if they commit to either:&#xD;
  &#xD;
                      -  Abstain continuously from heterosexual sexual intercourse as their preferred&#xD;
                         and usual lifestyle (abstinent on a long term and persistent basis) and&#xD;
                         agree to remain abstinent OR&#xD;
  &#xD;
                      -  To use birth control as follows:&#xD;
  &#xD;
                           -  Two methods of reliable birth control (one method that is highly&#xD;
                              effective and one additional effective (barrier) method), beginning 4&#xD;
                              weeks prior to initiating treatment with lenalidomide, during therapy,&#xD;
                              during dose interruptions and continuing for 4 weeks following&#xD;
                              discontinuation of lenalidomide treatment&#xD;
  &#xD;
            -  Male participants are eligible to participate if they agree to the following from the&#xD;
               time of first dose of study treatment until 28-days after the last dose of&#xD;
               lenalidomide, to allow for clearance of any altered sperm:&#xD;
  &#xD;
                 -  Refrain from donating sperm PLUS either:&#xD;
  &#xD;
                      -  Be abstinent from heterosexual intercourse as their preferred and usual&#xD;
                         lifestyle (abstinent on a long term and persistent basis) and agree to&#xD;
                         remain abstinent OR&#xD;
  &#xD;
                      -  Must agree to use contraception/barrier as detailed below:&#xD;
  &#xD;
                           -  Agree to use a male condom, even if they have undergone a successful&#xD;
                              vasectomy, and female partner to use an additional highly effective&#xD;
                              contraceptive method with a failure rate of &lt; 1% per year as when&#xD;
                              having sexual intercourse with a woman of childbearing potential&#xD;
                              (including pregnant females)&#xD;
  &#xD;
            -  Life expectancy ≥ 12 weeks&#xD;
  &#xD;
            -  Willing to return to enrolling institution for follow-up (during the Active Monitoring&#xD;
               Phase of the study)&#xD;
  &#xD;
            -  Willing to provide research bone marrow aspirate specimen&#xD;
  &#xD;
            -  Willing to follow the requirements of the Revlimid (Registered Trademark) Risk&#xD;
               Evaluation and Mitigation Strategy (REMS) program&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  History of any active malignancy within the past 2 years prior to screening, with the&#xD;
               exception of:&#xD;
  &#xD;
                 -  Adequately treated carcinoma in situ of the uterine cervix&#xD;
  &#xD;
                 -  Adequately treated basal cell carcinoma or localized squamous cell carcinoma of&#xD;
                    the skin&#xD;
  &#xD;
                 -  Asymptomatic prostate cancer with no requirement for therapy&#xD;
  &#xD;
                 -  Previous malignancy surgically resected (or treated with other modalities) with&#xD;
                    curative intent&#xD;
  &#xD;
            -  Other concurrent chemotherapy or any ancillary therapy considered investigational&#xD;
  &#xD;
                 -  NOTE: Bisphosphonates are considered to be supportive care rather than therapy,&#xD;
                    and are thus allowed while on protocol treatment&#xD;
  &#xD;
            -  Major surgery ≤ 14 days prior to study registration&#xD;
  &#xD;
            -  History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
               might confound the results of the trial, interfere with the subject's participation&#xD;
               for the full duration of the trial, or is not in the best interest of the subject to&#xD;
               participate, in the opinion of the treating investigator&#xD;
  &#xD;
            -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)&#xD;
  &#xD;
            -  Administration of strong/moderate CYP3A inhibitors or inducers ≤ 14 days OR 5&#xD;
               half-lives prior to registration, whichever is longer&#xD;
  &#xD;
            -  Known allergy to any of the study medications, their analogues, or excipients in the&#xD;
               various formulations of any agent&#xD;
  &#xD;
            -  Participation in other clinical trials, including those with other investigational&#xD;
               agents not included in this trial, ≤ 30 days prior to registration&#xD;
  &#xD;
            -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral&#xD;
               absorption or tolerance of venetoclax including difficulty swallowing&#xD;
  &#xD;
            -  Heart failure &gt; New York Heart Association (NYHA) class II&#xD;
  &#xD;
            -  Presence of positive hepatitis C antibody test result or positive hepatitis C&#xD;
               ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose&#xD;
               of study treatment&#xD;
  &#xD;
                 -  Note: Participants with positive hepatitis C antibody due to prior resolved&#xD;
                    disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is&#xD;
                    obtained&#xD;
  &#xD;
                 -  Note: Hepatitis RNA testing is optional and participants with negative hepatitis&#xD;
                    C antibody test are not required to also undergo hepatitis C RNA testing&#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>Shaji K. Kumar, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Mayo Clinic in Rochester</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Mayo Clinic in Rochester</name>
        <address>
          <city>Rochester</city>
          <state>Minnesota</state>
          <zip>55905</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Clinical Trials Referral Office</last_name>
        <phone>855-776-0015</phone>
        <email>mayocliniccancerstudies@mayo.edu</email>
      </contact>
      <investigator>
        <last_name>Shaji K. Kumar, M.D.</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://www.mayo.edu/research/clinical-trials</url>
      <description>Mayo Clinic Clinical Trials</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 12, 2023</study_first_submitted>
    <study_first_submitted_qc>September 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 15, 2023</last_update_submitted>
    <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 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>Multiple Myeloma</mesh_term>
      <mesh_term>Neoplasms, Plasma Cell</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>Lenalidomide</mesh_term>
      <mesh_term>Venetoclax</mesh_term>
      <mesh_term>Daratumumab</mesh_term>
      <mesh_term>Ichthammol</mesh_term>
      <mesh_term>BB 1101</mesh_term>
      <mesh_term>Antibodies, Monoclonal</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/NCT06042725
  org study id: MC210808
  secondary id: NCI-2023-06776
  secondary id: MC210808
  secondary id: 22-009930
  nct id: NCT06042725
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase I trial tests the safety, side effects, and best dose of venetoclax in combination
        with lenalidomide and dexamethasone, daratumumab and dexamethasone, or daratumumab,
        lenalidomide, and dexamethasone in treating patients with multiple myeloma. Venetoclax is in
        a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of
        cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Lenalidomide is a
        drug that is similar to thalidomide, and is used to treat multiple myeloma and certain types
        of anemia. Lenalidomide belongs to the family of drugs called angiogenesis inhibitors.
        Dexamethasone is in a class of medications called corticosteroids. It is used to reduce
        inflammation and lower the body's immune response to help lessen the side effects of
        chemotherapy drugs. 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. Adding venetoclax to the other drug combinations may allow control of the
        cancer than is possible with the current treatments.
  PRIMARY OBJECTIVE:
  
        I. To estimate the recommended phase II dose (RP2D) of venetoclax that can be combined with
        standard dose daratumumab and dexamethasone (Dd) (Arm A), lenalidomide and dexamethasone (Rd)
        (Arm B) or daratumumab, lenalidomide and dexamethasone (DRd) (Arm C) in patients with
        t(11;14) multiple myeloma (MM).
  
        SECONDARY OBJECTIVES:
  
        I. To assess frequency and severity of treatment-emergent adverse events (TEAEs) graded per
        National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
        version (v)5.0.
  
        II. To assess best response while on treatment per International Myeloma Working Group (IMWG)
        criteria.
  
        OUTLINE: This is a dose-escalation study of venetoclax. Patients with relapsed MM (Group 1)
        are assigned to Arm B or C. Patients with newly diagnosed MM (Group 2) are assigned to Arm A,
        B, or C.
  
        ARM A: Patients receive venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle,
        daratumumab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of
        cycles 3-6, and day 1 of cycles 7+, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12.
        Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or
        unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood
        samples during screening. In addition, patients undergo x-rays, whole-body low-dose computed
        tomography (WBLDCT), positron emission tomography (PET)/computed tomography (CT) or magnetic
        resonance imaging (MRI) scans during screening and on study, and bone marrow aspiration and
        biopsy during screening, and during follow-up
  
        ARM B: Patients receive venetoclax PO QD on days 1-28 of each cycle, lenalidomide PO QD on
        days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment
        repeats every 28 days for up to 36 cycles in the absence of disease progression or
        unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood
        samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans
        during screening and on study, and bone marrow aspiration and biopsy during screening, and
        during follow-up.
  
        ARM C: Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days
        1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+,
        lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22
        of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease
        progression or unacceptable toxicity. Patients also undergo chest x-ray and optional
        collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT,
        PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy
        during screening, on study, and during follow-up.
  
        After completion of study treatment, patients are followed up at 30 days and then every 3 or
        6 months for a total of 3 years.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose-limiting toxicity
  time frame: 28 Days (1 treatment cycle); Up to 3 years
  description: Dose-limiting toxicities (DLT) are defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
  measure: Frequency and severity of treatment-emergent adverse events
  time frame: Up to 30 days after completion of study treatment
  description: The number and severity of all adverse events (overall and by dose- level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group.
  measure: Best response while on treatment
  time frame: Up to 3 years
  description: The overall response rate and ≥ very good partial response (VGPR) rate will be estimated by the number of patients with each response category (e.g., stringent complete response, complete response, VGPR, partial response, etc) divided by the total number of evaluable patients.
  arm group label: Arm A (Ven-Dd)
  arm group type: Experimental
  description: Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up.
  arm group label: Arm B (Ven-Rd)
  arm group type: Experimental
  description: Patients receive venetoclax PO QD on days 1-28 of each cycle, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up.
  arm group label: Arm C (Ven-DRd)
  arm group type: Experimental
  description: Patients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, on study, and during follow-up.
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo optional collection of blood samples
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  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: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  intervention type: Procedure
  intervention name: Bone Marrow Biopsy
  description: Undergo bone marrow biopsy
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  other name: Biopsy of Bone Marrow
  other name: Biopsy, Bone Marrow
  intervention type: Procedure
  intervention name: Chest Radiography
  description: Undergo chest x-ray
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  other name: Chest X-ray
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo PET/CT
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  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: Biological
  intervention name: Daratumumab
  description: Given SC
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm C (Ven-DRd)
  other name: Anti-CD38 Monoclonal Antibody
  other name: Daratumumab Biosimilar HLX15
  other name: Daratumumab-fihj
  other name: Darzalex
  other name: HLX15
  other name: HuMax-CD38
  other name: JNJ-54767414
  intervention type: Drug
  intervention name: Dexamethasone
  description: Given PO
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  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: Drug
  intervention name: Lenalidomide
  description: Given PO
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  other name: CC-5013
  other name: CC5013
  other name: CDC 501
  other name: Revlimid
  intervention type: Procedure
  intervention name: Low Dose Computed Tomography of the Whole Body
  description: Undergo WBLDCT
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  other name: Low-dose Whole-body CT
  other name: Whole Body Low Dose Computed Tomography
  other name: Whole Body Low Dose CT
  other name: Whole-body Low-dose CT
  intervention type: Procedure
  intervention name: Magnetic Resonance Imaging
  description: Undergo MRI
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  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: Procedure
  intervention name: Positron Emission Tomography
  description: Undergo PET/CT
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  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: Drug
  intervention name: Venetoclax
  description: Given PO
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  other name: ABT-0199
  other name: ABT-199
  other name: ABT199
  other name: GDC-0199
  other name: RG7601
  other name: Venclexta
  other name: Venclyxto
  intervention type: Procedure
  intervention name: X-Ray Imaging
  description: Undergo x-rays
  arm group label: Arm A (Ven-Dd)
  arm group label: Arm B (Ven-Rd)
  arm group label: Arm C (Ven-DRd)
  other name: Conventional X-Ray
  other name: Diagnostic Radiology
  other name: Medical Imaging, X-Ray
  other name: Plain film radiographs
  other name: Radiographic Imaging
  other name: Radiographic imaging procedure (procedure)
  other name: Radiography
  other name: RG
  other name: Static X-Ray
  other name: X-Ray
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Shaji K. Kumar, M.D.
  role: Principal Investigator
  affiliation: Mayo Clinic in Rochester
  facility: 
  contact: 
  investigator: 
  country: United States
  url: https://www.mayo.edu/research/clinical-trials
  description: Mayo Clinic Clinical Trials
  responsible party type: Sponsor
  mesh term: Multiple Myeloma
  mesh term: Neoplasms, Plasma Cell
  mesh term: Dexamethasone
  mesh term: Dexamethasone acetate
  mesh term: Lenalidomide
  mesh term: Venetoclax
  mesh term: Daratumumab
  mesh term: Ichthammol
  mesh term: BB 1101
  mesh term: Antibodies, Monoclonal