Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03030261
Recruitment Status : Recruiting
First Posted : January 24, 2017
Last Update Posted : October 14, 2020
Sponsor:
Collaborators:
Bristol-Myers Squibb
Celgene
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE January 18, 2017
First Posted Date  ICMJE January 24, 2017
Last Update Posted Date October 14, 2020
Actual Study Start Date  ICMJE November 22, 2017
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
Event-free survival (EFS) rate [ Time Frame: 1 year ]
-Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2019)
  • Overall response rate (ORR) [ Time Frame: 1 year ]
    -Overall response rate (ORR) will be defined as the proportion of evaluable patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR).
  • Complete response rate (CRR) [ Time Frame: 1 year ]
    • Complete response rate (CRR) will be defined as the proportion of evaluable patients meeting the criteria complete (CR) or stringent complete response (sCR)
    • Stringent complete response (sCR) requires all of the following:
      • CR as defined below
      • Normal free light chain ratio (0.26-1.65)
      • Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
    • Complete response (CR) requires all of the following:
      • Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine
      • If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)
      • <5% plasma cells in the bone marrow
      • Disappearance of soft tissue plasmacytoma
    • Patients who do not meet the definition of CR based solely on residual monoclonal protein on serum electrophoresis and/or immunofixation, but are MRD-negative as described above, will also be considered CR.
  • Minimal residual disease negative (MRD-negative) rate [ Time Frame: 1 year ]
    -Minimal residual disease (MRD) testing should be performed using clonoSEQ next-generation sequencing technology [22]. Patients will be classified as MRD-negative or MRD-positive based on the current detection limits of the test (1 MM cell per 1x10^6 cells).
  • Event-free survival (EFS) [ Time Frame: Up to 5 years ]
    -Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.
  • Progression-free survival (PFS) [ Time Frame: Up to 5 years post completion of treatment ]
    -Progression-free survival (PFS) will be defined as time from ASCT to disease progression or relapse. Any patient who expires or withdraws prior to disease progression or relapse will be censored at last follow-up. Patients who are removed from study therapy prior to progression or relapse will be censored at the time of initiation of subsequent anti-myeloma treatment.
  • Overall survival (OS) [ Time Frame: Up to 5 years post completion of treatment ]
    -Overall survival (OS) will be defined as time from ASCT to death due to any causes. Patients who are alive at the time of data analyses will be censored on the last known alive date. Patients who are removed from study therapy prior death will be censored at the time of initiation of subsequent anti-myeloma treatment.
  • Toxicity of regimen as measured by frequency of adverse events per the number of participants treated [ Time Frame: Up to 30 days following completion of treatment (estimated to be 106 weeks) ]
    -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
  • Overall response rate (ORR) [ Time Frame: 1 year ]
    -Overall response rate (ORR) will be defined as the proportion of patients meeting the criteria for partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR).
  • Complete response rate (CRR) [ Time Frame: 1 year ]
    • Complete response rate (CRR) will be defined as the proportion of patients meeting the criteria complete (CR) or stringent complete response (sCR)
    • Stringent complete response (sCR) requires all of the following:
      • CR as defined below
      • Normal free light chain ratio (0.26-1.65)
      • Absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence
    • Complete response (CR) requires all of the following:
      • Disappearance of monoclonal protein by both protein electrophoresis and immunofixation studies from the blood and urine
      • If serum and urine monoclonal protein are unmeasurable, Normal free light chain ratio (0.26-1.65)
      • <5% plasma cells in the bone marrow
      • Disappearance of soft tissue plasmacytoma
    • Patients who do not meet the definition of CR based solely on residual monoclonal protein on serum electrophoresis and/or immunofixation, but are MRD-negative as described above, will also be considered CR.
  • Minimal residual disease negative (MRD-negative) rate [ Time Frame: 1 year ]
    -Minimal residual disease (MRD) testing should be performed using clonoSEQ next-generation sequencing technology [22]. Patients will be classified as MRD-negative or MRD-positive based on the current detection limits of the test (1 MM cell per 1x10^6 cells).
  • Event-free survival (EFS) [ Time Frame: 1 year ]
    -Event-free survival (EFS) will be defined as time from ASCT to disease progression, relapse, or death, whichever occurs first. Patients who are removed from study therapy prior to any of these events occurring will be censored at the time of initiation of subsequent anti-myeloma treatment.
  • Progression-free survival (PFS) [ Time Frame: Up to 5 years post completion of treatment ]
    -Progression-free survival (PFS) will be defined as time from ASCT to disease progression or relapse. Any patient who expires or withdraws prior to disease progression or relapse will be censored at last follow-up. Patients who are removed from study therapy prior to progression or relapse will be censored at the time of initiation of subsequent anti-myeloma treatment.
  • Overall survival (OS) [ Time Frame: Up to 5 years post completion of treatment ]
    -Overall survival (OS) will be defined as time from ASCT to death due to any causes. Patients who are alive at the time of data analyses will be censored on the last known alive date. Patients who are removed from study therapy prior death will be censored at the time of initiation of subsequent anti-myeloma treatment.
  • Toxicity of regimen as measured by frequency of adverse events per the number of participants treated [ Time Frame: Up to 30 days following completion of treatment (estimated to be 106 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma
Official Title  ICMJE A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma
Brief Summary

Based on the need to improve outcomes post second autologous stem cell transplant (ASCT) for multiple myeloma (MM) and the benefits seen of maintenance treatment following initial ASCT, the natural next step is to evaluate maintenance/continuation therapy following second ASCT.

Pomalidomide is active against MM cells refractory to both bortezomib and lenalidomide, making it an ideal choice for continuation therapy following second ASCT. Adding elotuzumab may increase efficacy and also the durability of responses which is essential to improving outcomes following second ASCT.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma in Relapse
Intervention  ICMJE
  • Drug: Elotuzumab
    During continuation therapy, elotuzumab will be administered on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 for Cycles 7+. For Cycles 1-6 elotuzumab will be administered intravenously at a dose of 10 mg/kg. For Cycles 7+ elotuzumab will be administered at a dose of 20 mg/kg.
    Other Name: Empliciti
  • Drug: Pomalidomide
    During continuation therapy, pomalidomide will be taken by mouth daily on Days 1-21 of each 28-day cycle at a starting dose of 2 mg. During continuation, pomalidomide may be dose escalated to 4 mg at the discretion of the treating physician if the 2 mg dose is tolerated.
    Other Name: Pomalyst
  • Drug: Dexamethasone
    During continuation therapy, dexamethasone will be taken by mouth at a starting dose of 40 mg. It will be given on a 28-day cycle as follows: on Days 1 and 15 for Cycles 1-6 and on Day 1 only for Cycles 7+. Sufficient quantity of drug for one cycle of therapy will be prescribed to the patient at a time.
    Other Name: Decadron
Study Arms  ICMJE Experimental: Elotuzumab + Pomalidomide + Dexamethasone
  • Patients will undergo standard of care ASCT melphalan conditioning. Administration of melphalan and the second ASCT will be done as part of routine care and procedures are not dictated by this protocol.
  • Continuation therapy with Elo-Pom-Dex will begin between Days 80 and 120 following the second ASCT:

    • Elotuzumab on Days 1 and 15 for Cycles 1-6 followed by 20 mg/kg on Day 1 for Cycles 7+
    • Pomalidomide daily on Days 1-21 of all cycles
    • Dexamethasone on Days 1 and 15 of all cycles
  • Continuation therapy may continue until relapse or progression.
Interventions:
  • Drug: Elotuzumab
  • Drug: Pomalidomide
  • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 20, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2026
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed diagnosis of multiple myeloma.
  • Received prior autologous stem cell transplantation as first line therapy for multiple myeloma with subsequent disease relapse/progression.
  • Failed 1 or 2 lines of treatment for multiple myeloma. A line of treatment includes all therapy including induction, transplant, and maintenance administered in a sequence in the absence of relapse/progression. Once relapse/progression occurs and subsequently the anti-myeloma treatment is changed, a new line of treatment has begun. Local radiation or corticosteroids will not be considered treatment for multiple myeloma.
  • Received 2 to 6 cycles of induction therapy per standard of care prior to 2nd autologous stem cell transplantation
  • Received standard of care melphalan conditioning for 2nd autologous stem cell transplantation, is currently Day +80 to +120 following transplant, and is responding to therapy (partial response or better as compared to pre-induction assessment.
  • All US study participants must be registered into the mandatory POMALYST REMS® program and be willing and able to comply with the requirements of the POMALYST REMS® program. For Canadian sites, patients will followed according to the Pomalidomide pregnancy prevention program
  • Females of reproductive potential within the US must agree to adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program. For Canadian sites, patients will followed according to the Pomalidomide pregnancy prevention program
  • Candidate for second autologous stem cell transplantation per local institution's guidelines with at least 2x106/kg CD34+ autologous stem cells available for transplantation.
  • At least 18 and no more than 75 years of age at enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Normal bone marrow and organ function as defined as ALL of the following:

    • Absolute neutrophil count ≥ 1000/mm^3
    • Platelets ≥ 75,000/mm^3 (transfusions not permitted within 7 days of screening)
    • Total bilirubin ≤ 2.0 x institutional upper limit of normal (IULN)
    • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
    • Creatinine clearance ≥ 15 mL/min
  • Females of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document.

Exclusion Criteria:

  • Prior exposure to elotuzumab or pomalidomide.
  • More than one prior transplant prior to study entry with the exception of tandem transplantation. Tandem transplantation is defined as two autologous stem cell transplants that occur within 9 months of one another, and the patient did not have disease progression in the period between the two transplants.
  • Presence of peripheral neuropathy ≥ grade 3 based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0
  • History of plasma cell leukemia or MM central nervous system (CNS) involvement.
  • Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
  • Diagnosed with another concurrent malignancy requiring treatment.
  • Known HIV or active hepatitis A, B, or C. Antidoby testing not required for screening
  • Known hypersensitivity to pomalidomide, dexamethasone, or any excipients in elotuzumab, formulation, or recombinant protein
  • Receiving any other investigational agents within 14 days prior to enrollment.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Females of childbearing potential must have two negative pregnancy tests. The first test should be performed within 10-14 days of study entry, and the second test within 24 hours prior to prescribing pomalidomide.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ravi Vij, M.D. (314) 454-8323 rvij@wustl.edu
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03030261
Other Study ID Numbers  ICMJE 201701084
CA204-225 ( Other Identifier: Bristol-Myers Squibb )
PO-CL-MM-PI-008341 ( Other Identifier: Celgene )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE
  • Bristol-Myers Squibb
  • Celgene
Investigators  ICMJE
Principal Investigator: Ravi Vij, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP