Clinical Trials /

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

NCT03030261

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma
  • Official Title: A Phase II Study of Elotuzumab, Pomalidomide, & Dexamethasone (Elo-Pom-Dex) With Second Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 201701084
  • SECONDARY ID: CA204-225
  • SECONDARY ID: PO-CL-MM-PI-008341
  • NCT ID: NCT03030261

Conditions

  • Multiple Myeloma in Relapse

Interventions

DrugSynonymsArms
ElotuzumabEmplicitiElotuzumab + Pomalidomide + Dexamethasone + ASCT
PomalidomidePomalystElotuzumab + Pomalidomide + Dexamethasone + ASCT
DexamethasoneDecadronElotuzumab + Pomalidomide + Dexamethasone + ASCT
MelphalanElotuzumab + Pomalidomide + Dexamethasone + ASCT

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Elotuzumab + Pomalidomide + Dexamethasone + ASCTExperimental(4) 28-day cycles of Elo-Pom-Dex induction: Elotuzumab on Days 1, 8, 15, and 22 for Cycles 1-2 and on Days 1 and 15 for Cycles 3-4 Pomalidomide daily on Days 1-21 of all cycles Dexamethasone on Days 1, 8, 15, and 22 of all cycles Following Elo-Pom-Dex induction, 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.
  • Elotuzumab
  • Pomalidomide
  • Dexamethasone
  • Melphalan

Eligibility Criteria

        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.

          -  Currently undergoing 2nd or 3rd line 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. Patients may have received 1-2 cycles of salvage
             therapy, local radiation, and/or corticosteroids as part of 2nd or 3rd line treatment
             prior to study entry if there was no further disease progression following
             administration.

          -  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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Event-free survival (EFS) rate
Time Frame:1 year
Safety Issue:
Description:-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.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:-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).
Measure:Complete response rate (CRR)
Time Frame:1 year
Safety Issue:
Description: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.
Measure:Minimal residual disease negative (MRD-negative) rate
Time Frame:1 year
Safety Issue:
Description:-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).
Measure:Event-free survival (EFS)
Time Frame:Up to 5 years
Safety Issue:
Description:-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.
Measure:Progression-free survival (PFS)
Time Frame:Up to 5 years post completion of treatment
Safety Issue:
Description:-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.
Measure:Overall survival (OS)
Time Frame:Up to 5 years post completion of treatment
Safety Issue:
Description:-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.
Measure: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)
Safety Issue:
Description:-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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

November 27, 2019