<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/NCT01690143</url>
  </required_header>
  <id_info>
    <org_study_id>CTO 101669</org_study_id>
    <secondary_id>Onyx IST-CAR-536</secondary_id>
    <nct_id>NCT01690143</nct_id>
  </id_info>
  <brief_title>Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation</brief_title>
  <official_title>Phase 1/2A Study Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Alabama at Birmingham</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is for patients that have multiple myeloma that has come back or relapsed and&#xD;
      their condition indicates a procedure called an Autologous Hematopoietic Stem Cell&#xD;
      Transplantation (AHSCT). AHSCT is a procedure when stem cells from bone marrow or blood are&#xD;
      removed before high-dose chemotherapy. Afterwards, the removed stem cells are put back into&#xD;
      the patient's body to form a new population of blood cells.&#xD;
&#xD;
      The high-dose chemotherapy administered before the AHSCT is called &quot;Conditioning Therapy.&quot;&#xD;
      The FDA has approved the use of the drug melphalan as a conditioning therapy. This research&#xD;
      study will look at whether adding the study drug called carfilzomib will improve participant&#xD;
      outcomes. Carfilzomib is considered investigational and is not approved by the FDA for the&#xD;
      treatment of relapsed multiple myeloma.&#xD;
&#xD;
      This study is divided into two phases.&#xD;
&#xD;
      Phase I: Dose Escalation Phase:&#xD;
&#xD;
      The main purpose of Part I of this study is to examine the safety of the study drug,&#xD;
      carfilzomib, and determine the safest amount of the study drug that can be given to subjects&#xD;
      who have multiple myeloma. Subjects on this study will receive different dose levels of the&#xD;
      study drug. If you are one of the first three subjects to receive the study drug, it will be&#xD;
      at what is called the 'starting dose' for the study which is the lowest dose that is expected&#xD;
      to be tolerated based on prior research. After the first set of participants receive the&#xD;
      study drug, the study doctor will review their health to see how they are tolerating the&#xD;
      treatment. This will decide if the study drug dosage will be increased or decreased for the&#xD;
      next set of subjects who join the study. It is anticipated that 12- 18 participants will&#xD;
      enroll in the Phase I portion of this study.&#xD;
&#xD;
      Phase II: Safety Confirmation Phase:&#xD;
&#xD;
      Once the study doctor has discovered the highest possible dose of study drug that subjects&#xD;
      can tolerate, up to 28 more subjects may be enrolled at that dose level. The main purpose of&#xD;
      the Phase II portion of the study is look at how effective the combination of carfilzomib and&#xD;
      melphalan when given before your stem cell transplantation is in treating multiple myeloma.&#xD;
      This expansion phase will also include evaluation of two single agent carfilzomib maintenance&#xD;
      therapy regimens for patients without disease progression at day 100.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase 1/2a trial. Since this is an AHSCT conditioning regimen trial, only one cycle&#xD;
      of therapy will be administered for each subject.&#xD;
&#xD;
      PHASE 1 The phase 1 component has a typical 3+3 design.&#xD;
&#xD;
        -  Initially up to three subjects will be enrolled in each cohort starting at cohort 0 in&#xD;
           the table below.&#xD;
&#xD;
        -  If no dose limiting toxicity (DLT) is noted among the 3 initial subjects, 3 additional&#xD;
           patients will be accrued at the subsequent cohort.&#xD;
&#xD;
        -  If 1/3 subjects experience DLT, 3 additional subjects will be accrued at the cohort. If&#xD;
           no additional DLT occur, accrual will continue at the subsequent cohort.&#xD;
&#xD;
        -  If 2 or more subjects experience DLT in a given cohort, the dose will be considered&#xD;
           higher than the maximum tolerated dose (MTD) and the immediately lower dose will be&#xD;
           considered the MTD.&#xD;
&#xD;
        -  If accrual is completed in cohort 4 with 0/3 or 1/6 DLT, the MTD will be considered &quot;not&#xD;
           reached&quot; and cohort 4 will be expanded in the phase 2 of the trial.&#xD;
&#xD;
        -  If 2 subjects experience DLTs in cohort 0, patients will be accrued in cohort -1, one&#xD;
           subject at a time, with the subsequent subject only being accrued once the current&#xD;
           subject has completed the DLT period (transplant day 30). The doses in cohort -1 will be&#xD;
           considered the MTD if 0/3 or 1/6 subjects experience DLT.&#xD;
&#xD;
        -  If ≥ 2 subjects experience DLT in cohort -1 the study will be interrupted without&#xD;
           proceeding to phase 2a and the combination of carfilzomib and high dose melphalan will&#xD;
           be considered too toxic.&#xD;
&#xD;
      PHASE 2 Once the MTD for the combination of carfilzomib and high dose melphalan with AHSCT is&#xD;
      found, there will be expansion of the MTD cohort so that 28 individuals will be treated at&#xD;
      the MTD of carfilzomib and high dose melphalan.&#xD;
&#xD;
      Screening - Subjects likely to meet eligibility criteria will be offered participation in the&#xD;
      study after the investigator verifies with the registration system that there is a current&#xD;
      available slot (phase 1). Subjects will sign informed consent prior to any protocol&#xD;
      associated procedure. Screening procedures are outlined in Table 3 and will 1) ensure that&#xD;
      subject meets all the eligibility criteria, 2) obtain disease assessment to allow efficacy&#xD;
      measurements, 3) assess baseline toxicity and 4) provide initial biological samples for&#xD;
      pharmacodynamic and correlative studies.&#xD;
&#xD;
      Treatment- Subjects will receive the appropriate dose of carfilzomib (according to assigned&#xD;
      cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will&#xD;
      be infused over 30 minutes. On day -2, with 60 to 120 minutes of the end of infusion of&#xD;
      carfilzomib, subjects will receive 200 mg/m2 of intravenous melphalan as an intravenous push&#xD;
      or a fast infusion. Prophylaxis of chemotherapy induced nausea and vomiting will follow&#xD;
      institutional guidelines.&#xD;
&#xD;
      Infusion of autologous cells- Infusion of autologous hematopoietic stem cells will occur on&#xD;
      day 0 and follow institutional SOP.&#xD;
&#xD;
      Follow up phase - On day 1 following HSCT patients will receive pegfilgrastim 6 mg&#xD;
      subcutaneously as per institutional standard of care aiming at faster engraftment. The follow&#xD;
      up phase will last 100 days and will consist of standard post transplantation supportive care&#xD;
      and monitoring of adverse events (AE's). For the phase 1 component of the study,&#xD;
      dose-limiting toxicities will be captured during the first 30 days after transplantation (DLT&#xD;
      period). Patients without progression may continue with carfilzomib maintenance therapy.&#xD;
&#xD;
      Patients will either be randomized in blocks of two to either maintenance therapy Arm 1= AB&#xD;
      (two cycles of A followed by two cycles of B), or maintenance therapy Arm 2= BA (two cycles&#xD;
      of B followed by two cycles of A). Maintenance regimen A will consist of carfilzomib 36 mg/m2&#xD;
      infused over 30 minutes on days 1,8,15. Maintenance regimen B will consist of carfilzomib 36&#xD;
      mg/m2 infused over 30 minutes on days 1, 2, 15 and 16. Each cycle will have 4 week duration.&#xD;
      The first four maintenance therapy cycles will be dictated by a randomized assignment at time&#xD;
      of study registration to maintenance therapy. For both maintenance therapy arms, a patient&#xD;
      preference questionnaire will be administered to the patient upon completion of the 4th&#xD;
      cycle. The remaining 8 cycles (cycles 5-12) will be administered according to the regimen&#xD;
      schedule preferred by the patient as documented on the patient preference questionnaire.&#xD;
&#xD;
      Disease assessment- Disease assessment will occur at day 100 (+/- 7 days) and will consist of&#xD;
      serum protein electrophoresis, serum and urine immunofixation, 24h urine protein&#xD;
      electrophoresis, serum free light chains, bone marrow aspiration and biopsy, complete blood&#xD;
      counts and metabolic panel.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2012</start_date>
  <completion_date type="Actual">November 1, 2017</completion_date>
  <primary_completion_date type="Actual">November 1, 2017</primary_completion_date>
  <phase>Phase 1/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>Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study]</measure>
    <time_frame>Up to 4 1/2 months</time_frame>
    <description>The maximum tolerated dose of carfilzomib that can be safely combined with high dose melphalan as conditioning regimen prior to autologous hematopoietic cell transplantation in patients with relapsed multiple myeloma meeting eligibility criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Very Good Partial Response (VGPR) Rate.</measure>
    <time_frame>Up to 17 months</time_frame>
    <description>VGPR defined as any one of the following:&#xD;
≥ 90% reduction of serum M-protein; ≥ 90% reduction in 24-hour urinary M-protein or decrease to &lt; 100 mg per 24 hour; ≥ 50% decrease in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio; ≥ 50% reduction in bone marrow plasma cells; ≥ 50% reduction in the size of soft tissue plasmacytomas.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Complete Response (CR) Rate.</measure>
    <time_frame>Up to 17 months</time_frame>
    <description>CR defined as the following: Negative immunofixation of the serum and urine. If only the measurable non-bone marrow parameter was free light chain, normalization of free light chain ratio. &lt; 5% plasma cells in bone marrow. And, disappearance of any soft tissue plasmacytomas.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Time for Neutrophil and Platelet Engraftment.</measure>
    <time_frame>Up to 1 month.</time_frame>
    <description>Neutrophil engraftment is defined as the first of three consecutive days with absolute neutrophil count &gt;500/mm3. Platelet engraftment is defined as the first of 3 consecutive days of platelets &gt; 20,000/mm3 without platelet transfusion in the prior 7 days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequency of Grades 3 and 4 Non-hematologic Adverse Events During the Transplant Component ( 135 Days)</measure>
    <time_frame>Up to 4 1/2 months</time_frame>
    <description>Grading of AE's is performed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Carfilzomib + high dose melphalan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.</description>
    <arm_group_label>Carfilzomib + high dose melphalan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Melphalan</intervention_name>
    <description>Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.</description>
    <arm_group_label>Carfilzomib + high dose melphalan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years and ≤ 70 years&#xD;
&#xD;
          2. Life expectancy ≥ 12 months&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2&#xD;
&#xD;
          4. Diagnosis of symptomatic multiple myeloma, relapsed after initial therapy.&#xD;
&#xD;
          5. At least minimal response (defined as 25% decrease in the M protein in serum or urine)&#xD;
             to the most recent treatment regimen.&#xD;
&#xD;
          6. Evaluable disease prior to most recent treatment regimen as defined by at least one of&#xD;
             the following:&#xD;
&#xD;
               -  Serum monoclonal (M) protein ≥0.5 g/dl by protein electrophoresis&#xD;
&#xD;
                    -  200 mg of M protein in the urine on 24 hour electrophoresis&#xD;
&#xD;
               -  Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin&#xD;
                  kappa to lambda free light chain ratio&#xD;
&#xD;
               -  Monoclonal bone marrow plasmacytosis ≥30%&#xD;
&#xD;
          7. Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and&#xD;
             serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to start of therapy&#xD;
&#xD;
          8. Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to registration (subjects may be&#xD;
             receiving red blood cell [RBC] transfusions in accordance with institutional&#xD;
             guidelines)&#xD;
&#xD;
          9. Creatinine clearance (CrCl) ≥ 40 mL/minute within 14 days prior to registration,&#xD;
             either measured or calculated using a standard formula (eg, Cockcroft and Gault).&#xD;
&#xD;
         10. Prior storage of at least 2 x 106 CD34+ cells/kg available for autologous&#xD;
             transplantation. During the phase 1 component of the study, at least the same amount&#xD;
             of cells is required as &quot;back up&quot; in the unlikely event of non-engraftment.&#xD;
&#xD;
         11. Subjects may have had a prior AHSCT for the treatment of MM as long as it was&#xD;
             performed greater than 12 months from study registration.&#xD;
&#xD;
         12. Subjects must meet institutional general eligibility criteria for autologous&#xD;
             transplantation.&#xD;
&#xD;
         13. Written informed consent in accordance with federal, local, and institutional&#xD;
             guidelines.&#xD;
&#xD;
         14. Female of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to&#xD;
             practice contraception.&#xD;
&#xD;
         15. Male subjects must agree to practice contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant or lactating females.&#xD;
&#xD;
          2. Major surgery within 30 days prior to start of treatment.&#xD;
&#xD;
          3. Acute active infection requiring treatment (systemic antibiotics, antivirals, or&#xD;
             antifungals) within 14 days prior to registration.&#xD;
&#xD;
          4. Known human immunodeficiency virus infection.&#xD;
&#xD;
          5. Active hepatitis B or C infection.&#xD;
&#xD;
          6. Unstable angina or myocardial infarction within 4 months prior to registration, NYHA&#xD;
             Class III or IV heart failure, uncontrolled angina, history of severe coronary artery&#xD;
             disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or&#xD;
             electrocardiographic evidence of acute ischemia or Grade 3 conduction system&#xD;
             abnormalities unless subject has a pacemaker.&#xD;
&#xD;
          7. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to&#xD;
             registration.&#xD;
&#xD;
          8. Nonhematologic malignancy within the past 3 years with the exception of a) adequately&#xD;
             treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)&#xD;
             carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or&#xD;
             less with stable prostate-specific antigen levels; or d) cancer considered cured by&#xD;
             surgical resection or unlikely to impact survival during the duration of the study,&#xD;
             such as localized transitional cell carcinoma of the bladder or benign tumors of the&#xD;
             adrenal or pancreas.&#xD;
&#xD;
          9. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to&#xD;
             registration.&#xD;
&#xD;
         10. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize&#xD;
             carfilzomib).&#xD;
&#xD;
         11. Subjects with pleural effusions requiring thoracentesis or ascites requiring&#xD;
             paracentesis within 14 days prior to registration.&#xD;
&#xD;
         12. Any other clinically significant medical disease or condition that, in the&#xD;
             Investigator's opinion, may interfere with protocol adherence or a subject's ability&#xD;
             to give informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luciano Costa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UAB</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina Hollings Cancer Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Costa LJ, Landau HJ, Chhabra S, Hari P, Innis-Shelton R, Godby KN, Hamadani M, Tamari R, Anderton K, Dixon P, Giralt SA. Phase 1/2 Trial of Carfilzomib Plus High-Dose Melphalan Preparative Regimen for Salvage Autologous Hematopoietic Cell Transplantation Followed by Maintenance Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma. Biol Blood Marrow Transplant. 2018 Jul;24(7):1379-1385. doi: 10.1016/j.bbmt.2018.01.036. Epub 2018 Feb 2.</citation>
    <PMID>29410301</PMID>
  </results_reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>July 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>March 21, 2018</results_first_submitted>
  <results_first_submitted_qc>June 12, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">July 10, 2018</results_first_posted>
  <last_update_submitted>July 9, 2018</last_update_submitted>
  <last_update_submitted_qc>July 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Luciano Jose Costa, MD</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </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>Melphalan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 21, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT01690143/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 21, 2014</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT01690143/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Carfilzomib + High Dose Melphalan</title>
          <description>Single arm.&#xD;
Carfilzomib: Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.&#xD;
Melphalan: Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients with relapsed multiple myeloma, candidates for autologous hematopoietic cell transplantation</population>
      <group_list>
        <group group_id="B1">
          <title>Carfilzomib + High Dose Melphalan</title>
          <description>Single arm.&#xD;
Carfilzomib: Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.&#xD;
Melphalan: Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Time in years from birth to enrollment</description>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="58" lower_limit="41" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Non-Hispanic Whites</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Hispanic Blacks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study]</title>
        <description>The maximum tolerated dose of carfilzomib that can be safely combined with high dose melphalan as conditioning regimen prior to autologous hematopoietic cell transplantation in patients with relapsed multiple myeloma meeting eligibility criteria.</description>
        <time_frame>Up to 4 1/2 months</time_frame>
        <population>Patients who underwent transplantation during phase 1</population>
        <group_list>
          <group group_id="O1">
            <title>Patients Undergoing Transplantation</title>
            <description>All patients who receive transplant in the phase 1 of the study</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study]</title>
          <description>The maximum tolerated dose of carfilzomib that can be safely combined with high dose melphalan as conditioning regimen prior to autologous hematopoietic cell transplantation in patients with relapsed multiple myeloma meeting eligibility criteria.</description>
          <population>Patients who underwent transplantation during phase 1</population>
          <units>mg/m2</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Very Good Partial Response (VGPR) Rate.</title>
        <description>VGPR defined as any one of the following:&#xD;
≥ 90% reduction of serum M-protein; ≥ 90% reduction in 24-hour urinary M-protein or decrease to &lt; 100 mg per 24 hour; ≥ 50% decrease in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio; ≥ 50% reduction in bone marrow plasma cells; ≥ 50% reduction in the size of soft tissue plasmacytomas.</description>
        <time_frame>Up to 17 months</time_frame>
        <population>All patients who underwent transplantation</population>
        <group_list>
          <group group_id="O1">
            <title>Patients Undergoing Transplantation</title>
            <description>All patients who receive transplant in the phase 1+2 of the study</description>
          </group>
        </group_list>
        <measure>
          <title>Very Good Partial Response (VGPR) Rate.</title>
          <description>VGPR defined as any one of the following:&#xD;
≥ 90% reduction of serum M-protein; ≥ 90% reduction in 24-hour urinary M-protein or decrease to &lt; 100 mg per 24 hour; ≥ 50% decrease in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio; ≥ 50% reduction in bone marrow plasma cells; ≥ 50% reduction in the size of soft tissue plasmacytomas.</description>
          <population>All patients who underwent transplantation</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Complete Response (CR) Rate.</title>
        <description>CR defined as the following: Negative immunofixation of the serum and urine. If only the measurable non-bone marrow parameter was free light chain, normalization of free light chain ratio. &lt; 5% plasma cells in bone marrow. And, disappearance of any soft tissue plasmacytomas.</description>
        <time_frame>Up to 17 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients Undergoing Transplantation</title>
            <description>All patients who receive transplant in the phase 1+2 of the study</description>
          </group>
        </group_list>
        <measure>
          <title>Complete Response (CR) Rate.</title>
          <description>CR defined as the following: Negative immunofixation of the serum and urine. If only the measurable non-bone marrow parameter was free light chain, normalization of free light chain ratio. &lt; 5% plasma cells in bone marrow. And, disappearance of any soft tissue plasmacytomas.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Median Time for Neutrophil and Platelet Engraftment.</title>
        <description>Neutrophil engraftment is defined as the first of three consecutive days with absolute neutrophil count &gt;500/mm3. Platelet engraftment is defined as the first of 3 consecutive days of platelets &gt; 20,000/mm3 without platelet transfusion in the prior 7 days.</description>
        <time_frame>Up to 1 month.</time_frame>
        <population>All patients</population>
        <group_list>
          <group group_id="O1">
            <title>Patients Undergoing Transplantation</title>
            <description>All patients who receive transplant in the phase 1+2 of the study</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time for Neutrophil and Platelet Engraftment.</title>
          <description>Neutrophil engraftment is defined as the first of three consecutive days with absolute neutrophil count &gt;500/mm3. Platelet engraftment is defined as the first of 3 consecutive days of platelets &gt; 20,000/mm3 without platelet transfusion in the prior 7 days.</description>
          <population>All patients</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10" lower_limit="8" upper_limit="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Frequency of Grades 3 and 4 Non-hematologic Adverse Events During the Transplant Component ( 135 Days)</title>
        <description>Grading of AE's is performed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
        <time_frame>Up to 4 1/2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Patients Undergoing Transplantation</title>
            <description>All patients who receive transplant in the phase 1+2 of the study</description>
          </group>
        </group_list>
        <measure>
          <title>Frequency of Grades 3 and 4 Non-hematologic Adverse Events During the Transplant Component ( 135 Days)</title>
          <description>Grading of AE's is performed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Patients Undergoing Transplantation</title>
          <description>All patients who receive transplant in the phase 1+2 of the study</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="44"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>heart failure</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>renal failure</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>hyperkalemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>diarrhea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="17" subjects_affected="17" subjects_at_risk="44"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Luciano J Costa, Principal Investigator</name_or_title>
      <organization>University of Alabama at Birmingham</organization>
      <phone>205-209-6038</phone>
      <email>ljcosta@uabmc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01690143
org study id: CTO 101669
secondary id: Onyx IST-CAR-536
nct id: NCT01690143
lead sponsor: 
collaborator: 
has dmc: Yes
This study is for patients that have multiple myeloma that has come back or relapsed and
      their condition indicates a procedure called an Autologous Hematopoietic Stem Cell
      Transplantation (AHSCT). AHSCT is a procedure when stem cells from bone marrow or blood are
      removed before high-dose chemotherapy. Afterwards, the removed stem cells are put back into
      the patient's body to form a new population of blood cells.

      The high-dose chemotherapy administered before the AHSCT is called "Conditioning Therapy."
      The FDA has approved the use of the drug melphalan as a conditioning therapy. This research
      study will look at whether adding the study drug called carfilzomib will improve participant
      outcomes. Carfilzomib is considered investigational and is not approved by the FDA for the
      treatment of relapsed multiple myeloma.

      This study is divided into two phases.

      Phase I: Dose Escalation Phase:

      The main purpose of Part I of this study is to examine the safety of the study drug,
      carfilzomib, and determine the safest amount of the study drug that can be given to subjects
      who have multiple myeloma. Subjects on this study will receive different dose levels of the
      study drug. If you are one of the first three subjects to receive the study drug, it will be
      at what is called the 'starting dose' for the study which is the lowest dose that is expected
      to be tolerated based on prior research. After the first set of participants receive the
      study drug, the study doctor will review their health to see how they are tolerating the
      treatment. This will decide if the study drug dosage will be increased or decreased for the
      next set of subjects who join the study. It is anticipated that 12- 18 participants will
      enroll in the Phase I portion of this study.

      Phase II: Safety Confirmation Phase:

      Once the study doctor has discovered the highest possible dose of study drug that subjects
      can tolerate, up to 28 more subjects may be enrolled at that dose level. The main purpose of
      the Phase II portion of the study is look at how effective the combination of carfilzomib and
      melphalan when given before your stem cell transplantation is in treating multiple myeloma.
      This expansion phase will also include evaluation of two single agent carfilzomib maintenance
      therapy regimens for patients without disease progression at day 100.
This is a phase 1/2a trial. Since this is an AHSCT conditioning regimen trial, only one cycle
      of therapy will be administered for each subject.

      PHASE 1 The phase 1 component has a typical 3+3 design.

        -  Initially up to three subjects will be enrolled in each cohort starting at cohort 0 in
           the table below.

        -  If no dose limiting toxicity (DLT) is noted among the 3 initial subjects, 3 additional
           patients will be accrued at the subsequent cohort.

        -  If 1/3 subjects experience DLT, 3 additional subjects will be accrued at the cohort. If
           no additional DLT occur, accrual will continue at the subsequent cohort.

        -  If 2 or more subjects experience DLT in a given cohort, the dose will be considered
           higher than the maximum tolerated dose (MTD) and the immediately lower dose will be
           considered the MTD.

        -  If accrual is completed in cohort 4 with 0/3 or 1/6 DLT, the MTD will be considered "not
           reached" and cohort 4 will be expanded in the phase 2 of the trial.

        -  If 2 subjects experience DLTs in cohort 0, patients will be accrued in cohort -1, one
           subject at a time, with the subsequent subject only being accrued once the current
           subject has completed the DLT period (transplant day 30). The doses in cohort -1 will be
           considered the MTD if 0/3 or 1/6 subjects experience DLT.

        -  If ≥ 2 subjects experience DLT in cohort -1 the study will be interrupted without
           proceeding to phase 2a and the combination of carfilzomib and high dose melphalan will
           be considered too toxic.

      PHASE 2 Once the MTD for the combination of carfilzomib and high dose melphalan with AHSCT is
      found, there will be expansion of the MTD cohort so that 28 individuals will be treated at
      the MTD of carfilzomib and high dose melphalan.

      Screening - Subjects likely to meet eligibility criteria will be offered participation in the
      study after the investigator verifies with the registration system that there is a current
      available slot (phase 1). Subjects will sign informed consent prior to any protocol
      associated procedure. Screening procedures are outlined in Table 3 and will 1) ensure that
      subject meets all the eligibility criteria, 2) obtain disease assessment to allow efficacy
      measurements, 3) assess baseline toxicity and 4) provide initial biological samples for
      pharmacodynamic and correlative studies.

      Treatment- Subjects will receive the appropriate dose of carfilzomib (according to assigned
      cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will
      be infused over 30 minutes. On day -2, with 60 to 120 minutes of the end of infusion of
      carfilzomib, subjects will receive 200 mg/m2 of intravenous melphalan as an intravenous push
      or a fast infusion. Prophylaxis of chemotherapy induced nausea and vomiting will follow
      institutional guidelines.

      Infusion of autologous cells- Infusion of autologous hematopoietic stem cells will occur on
      day 0 and follow institutional SOP.

      Follow up phase - On day 1 following HSCT patients will receive pegfilgrastim 6 mg
      subcutaneously as per institutional standard of care aiming at faster engraftment. The follow
      up phase will last 100 days and will consist of standard post transplantation supportive care
      and monitoring of adverse events (AE's). For the phase 1 component of the study,
      dose-limiting toxicities will be captured during the first 30 days after transplantation (DLT
      period). Patients without progression may continue with carfilzomib maintenance therapy.

      Patients will either be randomized in blocks of two to either maintenance therapy Arm 1= AB
      (two cycles of A followed by two cycles of B), or maintenance therapy Arm 2= BA (two cycles
      of B followed by two cycles of A). Maintenance regimen A will consist of carfilzomib 36 mg/m2
      infused over 30 minutes on days 1,8,15. Maintenance regimen B will consist of carfilzomib 36
      mg/m2 infused over 30 minutes on days 1, 2, 15 and 16. Each cycle will have 4 week duration.
      The first four maintenance therapy cycles will be dictated by a randomized assignment at time
      of study registration to maintenance therapy. For both maintenance therapy arms, a patient
      preference questionnaire will be administered to the patient upon completion of the 4th
      cycle. The remaining 8 cycles (cycles 5-12) will be administered according to the regimen
      schedule preferred by the patient as documented on the patient preference questionnaire.

      Disease assessment- Disease assessment will occur at day 100 (+/- 7 days) and will consist of
      serum protein electrophoresis, serum and urine immunofixation, 24h urine protein
      electrophoresis, serum free light chains, bone marrow aspiration and biopsy, complete blood
      counts and metabolic panel.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study]
time frame: Up to 4 1/2 months
description: The maximum tolerated dose of carfilzomib that can be safely combined with high dose melphalan as conditioning regimen prior to autologous hematopoietic cell transplantation in patients with relapsed multiple myeloma meeting eligibility criteria.
measure: Very Good Partial Response (VGPR) Rate.
time frame: Up to 17 months
description: VGPR defined as any one of the following:
≥ 90% reduction of serum M-protein; ≥ 90% reduction in 24-hour urinary M-protein or decrease to < 100 mg per 24 hour; ≥ 50% decrease in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio; ≥ 50% reduction in bone marrow plasma cells; ≥ 50% reduction in the size of soft tissue plasmacytomas.
measure: Complete Response (CR) Rate.
time frame: Up to 17 months
description: CR defined as the following: Negative immunofixation of the serum and urine. If only the measurable non-bone marrow parameter was free light chain, normalization of free light chain ratio. < 5% plasma cells in bone marrow. And, disappearance of any soft tissue plasmacytomas.
measure: Median Time for Neutrophil and Platelet Engraftment.
time frame: Up to 1 month.
description: Neutrophil engraftment is defined as the first of three consecutive days with absolute neutrophil count >500/mm3. Platelet engraftment is defined as the first of 3 consecutive days of platelets > 20,000/mm3 without platelet transfusion in the prior 7 days.
measure: Frequency of Grades 3 and 4 Non-hematologic Adverse Events During the Transplant Component ( 135 Days)
time frame: Up to 4 1/2 months
description: Grading of AE's is performed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
arm group label: Carfilzomib + high dose melphalan
arm group type: Experimental
description: Single arm.
intervention type: Drug
intervention name: Carfilzomib
description: Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
arm group label: Carfilzomib + high dose melphalan
intervention type: Drug
intervention name: Melphalan
description: Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
arm group label: Carfilzomib + high dose melphalan
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Luciano Costa, MD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
facility: 
facility: 
facility: 
facility: 
country: United States
citation: Costa LJ, Landau HJ, Chhabra S, Hari P, Innis-Shelton R, Godby KN, Hamadani M, Tamari R, Anderton K, Dixon P, Giralt SA. Phase 1/2 Trial of Carfilzomib Plus High-Dose Melphalan Preparative Regimen for Salvage Autologous Hematopoietic Cell Transplantation Followed by Maintenance Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma. Biol Blood Marrow Transplant. 2018 Jul;24(7):1379-1385. doi: 10.1016/j.bbmt.2018.01.036. Epub 2018 Feb 2.
PMID: 29410301
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Luciano Jose Costa, MD
investigator title: Associate Professor of Medicine
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Melphalan
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 