<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/NCT03004287</url>
  </required_header>
  <id_info>
    <org_study_id>206241</org_study_id>
    <nct_id>NCT03004287</nct_id>
  </id_info>
  <brief_title>2015-12: A Study Exploring the Use of Early and Late Consolidation/Maintenance Therapy</brief_title>
  <official_title>2015-12: A Phase II Study Exploring the Use of Early and Late Consolidation/Maintenance With Anti-CD38 (Protein) Monoclonal Antibody to Improve Progression Free Survival in Patients With Newly Diagnosed Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arkansas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Janssen, LP</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Arkansas</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess whether adding one of the newest multiple myeloma therapies,&#xD;
      daratumumab, into the Total Therapy approach helps patients live longer with fewer side&#xD;
      effects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Past studies conducted at the Myeloma Institute and at other institutions have shown that&#xD;
      many patients with high-risk disease (as determined by gene array studies - studies that look&#xD;
      at specific genes using special equipment) tend to have shorter remissions (disappearance of&#xD;
      signs and symptoms of myeloma) and do not survive as long as participants with low-risk&#xD;
      myeloma. The Total Therapy approach to treatment carried out at the Myeloma Institute where&#xD;
      multiple chemotherapy agents are given as induction followed by a stem cell transplant,&#xD;
      post-transplant consolidation, and maintenance therapy has proven to be the best available&#xD;
      treatment strategy. However, the availability of new treatments that work in different ways&#xD;
      offers the possibility of improving the effectiveness of Total Therapy treatment while&#xD;
      potentially reducing the number of side effects patients' experience. Daratumumab is a human&#xD;
      monoclonal antibody or protein drug. It recognizes a specific protein, CD38, which is found&#xD;
      at high levels on multiple myeloma cells. An antibody is something that finds and kills&#xD;
      foreign objects in your body, in this case, myeloma cells. The other drugs that will be used&#xD;
      in the study treatment regimen include carfilzomib or bortezomib, thalidomide, lenalidomide,&#xD;
      dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide, lenalidomide and&#xD;
      dexamethasone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measure the progression-free survival in patients with high risk multiple myeloma</measure>
    <time_frame>48 months</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Study Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Induction Chemotherapy: Carfilzomib, Thalidomide, Dexamethasone, Daratumumab , CisPlatin, Adriamycin, Cyclophosphamide and Etoposide (KTD-Dara-PACE).&#xD;
Autologous Stem Cell Transplant (ASCT) 1: Melphalan, Dexamethasone, ASCT.&#xD;
Immunological Consolidation 1: Daratumumab.&#xD;
Consolidation 1: Daratumumab, Carfilzomib, Dexamethasone (Dara-KD).&#xD;
ASCT 2 (optional): Melphalan, Dexamethasone, ASCT.&#xD;
Immunological Consolidation 2: Daratumumab.&#xD;
Maintenance: Dara-KD alternating with Daratumumab, lenalidomide, and Dexamethasone (Dara-RD) in 3-month blocks.&#xD;
Bortezomib may be substituted for carfilzomib throughout the regimen at the discretion of the treating physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Given by vein: days 1 and 2 of Induction; days 1, 8, 15, and 22 of Consolidation 1; and days 1, 8, 15, and 22 of alternating 3-month blocks during Maintenance.</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Kyprolis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thalidomide</intervention_name>
    <description>Given by mouth at bedtime: days 1-4 of Induction</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Thalomid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Given by mouth or by vein: days 1-4 of Induction; days -4 - -1 of Transplant(s); and days 1, 8, 15, and 22 of every cycle during Maintenance</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Baycadron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Daratumumab</intervention_name>
    <description>Given by vein: day -1 of induction; days 1 and 8 of Immunological Consolidations; and day 1 of each Maintenance cycle</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Darzalex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given by vein: days 1-4 (continuous infusion) of Induction</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Platinol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adriamycin</intervention_name>
    <description>Given by vein: days 1-4 (continuous infusion) of Induction</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Doxorubicin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given by vein: days 1-4 (continuous infusion) of Induction</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Cytoxan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Given by vein: days 1-4 (continuous infusion) of Induction</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Eposin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Given by vein: days -4 - -1 of Transplant(s)</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>ASCT</intervention_name>
    <description>day 0 of Transplant(s)</description>
    <arm_group_label>Study Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenalidomide</intervention_name>
    <description>Given by mouth: days 1-21 of alternating 3-month blocks during Maintenance</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Revlimid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bortezomib</intervention_name>
    <description>Given by vein or subcutaneous injection: may be substituted for carfilzomib throughout the study regimen at the discretion of the treating physician</description>
    <arm_group_label>Study Treatment</arm_group_label>
    <other_name>Velcade</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have newly diagnosed active Multiple Myeloma (MM) requiring treatment.&#xD;
             Patients with a previous history of smoldering myeloma will be eligible if there is&#xD;
             evidence of progressive disease requiring chemotherapy.&#xD;
&#xD;
          -  Patients must be either untreated or have not received more than four cycles of&#xD;
             systemic MM therapy (e.g. Revlimid Dexamethasone (RD), Bortezomib Revlimid&#xD;
             Dexamethasone (VRD). Prior bisphosphonates and localized radiation are allowed.&#xD;
&#xD;
          -  Participants must have high-risk disease, as defined by at least one of the following:&#xD;
&#xD;
          -  Myeloma Prognostic Risk Signature (MyPRS) risk score ≥ 50.4&#xD;
&#xD;
          -  Lactate Dehydrogenase (LDH) ≥ 360 U/L (Rule out hemolysis and infection; contact PI if&#xD;
             any doubt.)&#xD;
&#xD;
          -  Diagnosis of primary plasma cell leukemia.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) ≤ 2, unless solely due to symptoms of&#xD;
             MM-related bone disease.&#xD;
&#xD;
          -  Patients must have a platelet count ≥ 50,000/μL, unless lower levels are explained by&#xD;
             extensive bone marrow plasmacytosis.&#xD;
&#xD;
          -  Patients must be at least 18 years of age and not older than 75 years of age at the&#xD;
             time of registration.&#xD;
&#xD;
          -  Participants must have a baseline serum creatinine level &lt; 3 mg/dL and baseline&#xD;
             Alanine Aminotransferase (ALT) &lt; 3x Upper Limit of Normal (ULN).&#xD;
&#xD;
          -  Participants must have an ejection fraction by echocardiogram (ECHO) or Multiple-gated&#xD;
             Acquisition Scan (MUGA) scan ≥ 45%&#xD;
&#xD;
          -  Patients must have adequate pulmonary function studies &gt; 50% of predicted on&#xD;
             mechanical aspects (Forced Expiratory Volume 1 (FEV1), Forced Vital Capacity (FVC) and&#xD;
             diffusion capacity (DLCO) &gt; 50% of predicted. If the patient is unable to complete&#xD;
             pulmonary function tests due to MM related pain or other conditions, an exception may&#xD;
             be granted if the principal investigator documents that the patient is a candidate for&#xD;
             high dose therapy.&#xD;
&#xD;
          -  Patients must have signed an Institutional Review Board (IRB)-approved informed&#xD;
             consent indicating their understanding of the proposed treatment and that the protocol&#xD;
             has been approved by the Institutional Review Board (IRB).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No evidence of high-risk disease&#xD;
&#xD;
          -  Poorly controlled hypertension, diabetes mellitus, active or uncontrolled hepatitis,&#xD;
             or other serious medical or psychiatric illness that could potentially interfere with&#xD;
             the completion of treatment according to this protocol.&#xD;
&#xD;
          -  Patients must not have prior malignancy, except for adequately treated basal cell or&#xD;
             squamous cell skin cancer, in situ cervical cancer, or other cancer for which the&#xD;
             patient has not received treatment for one year prior to enrollment. Other cancers&#xD;
             will only be acceptable if the patient's life expectancy exceeds five years.&#xD;
&#xD;
          -  Pregnant or nursing women may not participate. Women of childbearing potential must&#xD;
             have a negative pregnancy documented within one week of registration.&#xD;
&#xD;
          -  Subjects of reproductive potential may not participate unless they have agreed to use&#xD;
             an effective contraceptive method.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frits van Rhee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arkansas for Medical Science-Myeloma Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>July 12, 2023</last_update_submitted>
  <last_update_submitted_qc>July 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 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>Thalidomide</mesh_term>
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Melphalan</mesh_term>
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Lenalidomide</mesh_term>
    <mesh_term>Bortezomib</mesh_term>
    <mesh_term>Daratumumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03004287
org study id: 206241
nct id: NCT03004287
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study will assess whether adding one of the newest multiple myeloma therapies,
      daratumumab, into the Total Therapy approach helps patients live longer with fewer side
      effects
Past studies conducted at the Myeloma Institute and at other institutions have shown that
      many patients with high-risk disease (as determined by gene array studies - studies that look
      at specific genes using special equipment) tend to have shorter remissions (disappearance of
      signs and symptoms of myeloma) and do not survive as long as participants with low-risk
      myeloma. The Total Therapy approach to treatment carried out at the Myeloma Institute where
      multiple chemotherapy agents are given as induction followed by a stem cell transplant,
      post-transplant consolidation, and maintenance therapy has proven to be the best available
      treatment strategy. However, the availability of new treatments that work in different ways
      offers the possibility of improving the effectiveness of Total Therapy treatment while
      potentially reducing the number of side effects patients' experience. Daratumumab is a human
      monoclonal antibody or protein drug. It recognizes a specific protein, CD38, which is found
      at high levels on multiple myeloma cells. An antibody is something that finds and kills
      foreign objects in your body, in this case, myeloma cells. The other drugs that will be used
      in the study treatment regimen include carfilzomib or bortezomib, thalidomide, lenalidomide,
      dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide, lenalidomide and
      dexamethasone.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Measure the progression-free survival in patients with high risk multiple myeloma
time frame: 48 months
arm group label: Study Treatment
arm group type: Experimental
description: Induction Chemotherapy: Carfilzomib, Thalidomide, Dexamethasone, Daratumumab , CisPlatin, Adriamycin, Cyclophosphamide and Etoposide (KTD-Dara-PACE).
Autologous Stem Cell Transplant (ASCT) 1: Melphalan, Dexamethasone, ASCT.
Immunological Consolidation 1: Daratumumab.
Consolidation 1: Daratumumab, Carfilzomib, Dexamethasone (Dara-KD).
ASCT 2 (optional): Melphalan, Dexamethasone, ASCT.
Immunological Consolidation 2: Daratumumab.
Maintenance: Dara-KD alternating with Daratumumab, lenalidomide, and Dexamethasone (Dara-RD) in 3-month blocks.
Bortezomib may be substituted for carfilzomib throughout the regimen at the discretion of the treating physician.
intervention type: Drug
intervention name: Carfilzomib
description: Given by vein: days 1 and 2 of Induction; days 1, 8, 15, and 22 of Consolidation 1; and days 1, 8, 15, and 22 of alternating 3-month blocks during Maintenance.
arm group label: Study Treatment
other name: Kyprolis
intervention type: Drug
intervention name: Thalidomide
description: Given by mouth at bedtime: days 1-4 of Induction
arm group label: Study Treatment
other name: Thalomid
intervention type: Drug
intervention name: Dexamethasone
description: Given by mouth or by vein: days 1-4 of Induction; days -4 - -1 of Transplant(s); and days 1, 8, 15, and 22 of every cycle during Maintenance
arm group label: Study Treatment
other name: Baycadron
intervention type: Drug
intervention name: Daratumumab
description: Given by vein: day -1 of induction; days 1 and 8 of Immunological Consolidations; and day 1 of each Maintenance cycle
arm group label: Study Treatment
other name: Darzalex
intervention type: Drug
intervention name: Cisplatin
description: Given by vein: days 1-4 (continuous infusion) of Induction
arm group label: Study Treatment
other name: Platinol
intervention type: Drug
intervention name: Adriamycin
description: Given by vein: days 1-4 (continuous infusion) of Induction
arm group label: Study Treatment
other name: Doxorubicin
intervention type: Drug
intervention name: Cyclophosphamide
description: Given by vein: days 1-4 (continuous infusion) of Induction
arm group label: Study Treatment
other name: Cytoxan
intervention type: Drug
intervention name: Etoposide
description: Given by vein: days 1-4 (continuous infusion) of Induction
arm group label: Study Treatment
other name: Eposin
intervention type: Drug
intervention name: Melphalan
description: Given by vein: days -4 - -1 of Transplant(s)
arm group label: Study Treatment
intervention type: Procedure
intervention name: ASCT
description: day 0 of Transplant(s)
arm group label: Study Treatment
intervention type: Drug
intervention name: Lenalidomide
description: Given by mouth: days 1-21 of alternating 3-month blocks during Maintenance
arm group label: Study Treatment
other name: Revlimid
intervention type: Drug
intervention name: Bortezomib
description: Given by vein or subcutaneous injection: may be substituted for carfilzomib throughout the study regimen at the discretion of the treating physician
arm group label: Study Treatment
other name: Velcade
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Frits van Rhee, MD
role: Principal Investigator
affiliation: University of Arkansas for Medical Science-Myeloma Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Thalidomide
mesh term: Dexamethasone
mesh term: Cyclophosphamide
mesh term: Melphalan
mesh term: Doxorubicin
mesh term: Etoposide
mesh term: Lenalidomide
mesh term: Bortezomib
mesh term: Daratumumab
sharing ipd: No