Clinical Trials /

Elotuzumab, Lenalidomide and Dexamethasone in Treatment of Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients

NCT02843074

Description:

This is a phase 2, single arm, open-label, multicenter study to evaluate the feasibility and tolerance of the combination of elotuzumab, lenalidomide, and dexamethasone in the induction, consolidation, and maintenance treatment of transplant eligible, newly diagnosed multiple myeloma patients.

Related Conditions:
  • Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Elotuzumab, Lenalidomide and Dexamethasone in Treatment of Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients
  • Official Title: Phase 2 Study Assessing Feasibility and Tolerance of the Combination of Elotuzumab, Lenalidomide and Dexamethasone in Induction, Consolidation and Maintenance Treatment of Transplant-Eligible Patients Newly Diagnosed With Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: SCRI MM61
  • NCT ID: NCT02843074

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
elotuzumabEmplicitiERd Therapy
LenalidomideRevlimidERd Therapy
DexamethasoneDecadronERd Therapy

Purpose

This is a phase 2, single arm, open-label, multicenter study to evaluate the feasibility and tolerance of the combination of elotuzumab, lenalidomide, and dexamethasone in the induction, consolidation, and maintenance treatment of transplant eligible, newly diagnosed multiple myeloma patients.

Detailed Description

      The primary purpose of this study is to evaluate the feasibility of using the combination of
      elotuzumab, lenalidomide, and dexamethasone (ERd) as induction therapy and the ability of the
      combination to facilitate the start of autologous stem cell transplantation (ASCT) in
      transplant-eligible patients newly diagnosed with multiple myeloma. In addition to induction,
      the efficacy, safety, and tolerability of ERd as consolidation and maintenance therapy in
      these patients will be observed.

      Eligible patients will undergo four 28-day cycles of an induction regimen of elotuzumab,
      lenalidomide, and dexamethasone. Following completion of 4 cycles of induction therapy, all
      patients will undergo standard mobilization, collection of stem cells, and then ASCT using a
      melphalan conditioning regimen as per institutional guidelines.

      Toxicity evaluation will be interrupted during the stem cell procedure and will resume with
      the onset of consolidation. Adverse events will be collected, however, from the end of
      induction up to mobilization.

      Consolidation therapy will begin 70 to 120 days following ASCT and will consist of four
      28-day cycles of elotuzumab, lenalidomide, and dexamethasone. All patients that do not
      experience progressive disease will begin maintenance therapy of elotuzumab, lenalidomide,
      and dexamethasone. The duration of maintenance will be 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
ERd TherapyExperimentalINDUCTION: Cycles 1-2: elotuzumab 10mg/kg IV days 1, 8, 15, 22; lenalidomide (len) 25mg orally (PO), once daily (QD) on days 1-21; dexamethasone (dex) 28 mg PO (3-24 hrs before elotuzumab IV) and 8mg IV (45-90 minutes before elotuzumab) days 1, 8, 15, 22. Cycles 3-4: elotuzumab 10mg/kg IV days 1 and 15; len 25mg PO QD days 1-21; dex 8mg PO (3-24 hrs before elotuzumab IV) and 8mg IV (45-90 minutes before elotuzumab) days 1 and 15; dex 40mg PO days 8 and 22. CONSOLIDATION: Four 28-day cycles: elotuzumab 10mg/kg IV days 1 and 15; len 15mg PO QD days 1-21; dex 28mg PO (3-24 hrs before elotuzumab) and 8mg IV (45-90 minutes before elotuzumab) days 1 and 15; dex 40mg PO days 8 and 22. MAINTENANCE: After completing consolidation therapy patients without progressive disease will receive, for up to 24 months, 28-day cycles of elotuzumab 20mg/kg IV day 1; len 10mg +/- 5mg PO QD days 1-21; dex 28mg PO (3-24 hrs before elotuzumab) and 8mg IV (45-90 minutes prior to elotuzumab) day 1.
  • elotuzumab
  • Lenalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Newly diagnosed myeloma requiring systemic chemotherapy as per International Myeloma
             Working Group (IMWG) uniform criteria and Diagnostic Criteria and Staging for Multiple
             Myeloma

               -  Ideally, no prior therapy, or

               -  No more than 1 cycle of therapy for emergent control of disease prior to
                  enrolling on study, including prior treatment of hypercalcemia, spinal cord
                  compression, or active and/or aggressively progressing myeloma with
                  corticosteroids or lenalidomide or bortezomib-based regimens (treatment dose
                  should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period,
                  or not more than 1 cycle)

               -  Bisphosphonates are permitted

          -  Eligible and plan to undergo ASCT in first remission

          -  Measurable disease, prior to initial treatment as indicated by one or more of the
             following:

               -  Serum M-protein ≥1.0 g/dL

               -  Urine M-protein ≥200 mg/24 hours

               -  Serum free light chain assay: involved free light chain level ≥10 mg/dL (≥100
                  mg/L) provided the serum free light chain ratio is abnormal.

          -  Ability to take aspirin or other venous thromboembolism (VTE) anticoagulant therapy

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 thru 2

          -  Adequate hematologic, renal, and liver function.

          -  All study participants must be registered into the mandatory Revlimid REMS® program
             and must be willing and able to comply with the requirements of that program.

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS® program.

          -  Male patients with female partners of childbearing potential and female patients of
             childbearing potential are required to use two forms of acceptable contraception,
             including one barrier method, during their participation in the study and for 28 days
             following last dose of study drugs. Male patients must also refrain from donating
             semen or sperm during their participation in the study.

          -  Willingness and ability to comply with study and follow-up procedures.

          -  Ability to understand the nature of this study and give written informed consent.

        Exclusion Criteria:

          -  Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes
             (POEMS) syndrome

          -  Plasma cell leukemia

          -  Waldenström's macroglobulinemia or IgM myeloma

          -  Presence of other active cancers, or history of treatment for invasive cancer ≤5
             years. Patients with Stage I cancer who have received definitive local treatment and
             are considered unlikely to recur are eligible. All patients with previously treated in
             situ carcinoma (i.e., non-invasive) are eligible, as are patients with a history of
             non-melanoma skin cancer.

          -  Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of
             protocol treatment (localized radiotherapy to a single site at least 1 week before
             start is permissible)

          -  Major surgical procedures ≤28 days of beginning study drug, or minor surgical
             procedures ≤7 days. No waiting required following port-a-cath placement.

          -  Acute active infection requiring systemic antibiotics, antivirals, or antifungals
             within 2 weeks prior to first dose of study treatment

          -  Presence of active gastrointestinal disease or other condition that will interfere
             significantly with the absorption, distribution, metabolism, or excretion of oral
             therapy (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2,
             and malabsorption syndrome)

          -  Any of the following cardiac diseases currently or within the last 6 months:

               -  Left ventricular ejection fraction (LVEF) <40% as determined by echocardiogram
                  (ECHO) or multiple-gated acquisition (MUGA) scan

               -  Unstable angina pectoris

               -  Congestive heart failure (New York Heart Association ≥ Grade 2

               -  Acute myocardial infarction

               -  Conduction abnormality not controlled with pacemaker or medication

               -  Significant ventricular or supraventricular arrhythmias (patients with chronic
                  rate-controlled atrial fibrillation in the absence of other cardiac abnormalities
                  are eligible)

               -  Valvular disease with significant compromise in cardiac function

          -  Known seropositive for or active viral infection with human immunodeficiency virus or
             hepatitis A, B, or C virus. Patients who are seropositive because of hepatitis B virus
             vaccine are eligible.

          -  Any clinically significant medical disease or condition that, in the treating
             Investigator's opinion, may interfere with protocol adherence or a patient's ability
             to give informed consent

          -  Pregnant or lactating females

          -  Contraindication to any of the required concomitant drugs, including dexamethasone, H1
             and H2 blockers, and acetaminophen, or if patient has a history of prior thrombotic
             disease, warfarin or low molecular weight heparin

          -  No health coverage, or if the copay for lenalidomide is not acceptable to the patient.

          -  Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Induction Feasibility Rate (IFR)
Time Frame:weekly for 16 weeks
Safety Issue:
Description:Defined as the percentage of patients who successfully complete four 28-day cycles of induction therapy with elotuzumab, lenalidomide and dexamethasone (ERd) and are able to start autologous stem cell transplantation (ASCT).

Secondary Outcome Measures

Measure:Complete Response Rate (CRR)
Time Frame:every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
Safety Issue:
Description:Defined as the percentage of patients who achieve a complete response (CR) or near complete response (nCR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per International Myeloma Working Group (IMWG) and European Group for Blood and Marrow Transplantation (EBMT) criteria.
Measure:Overall Response Rate (ORR)
Time Frame:every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
Safety Issue:
Description:Defined as the percentage of patients who achieve at least a partial response (PR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per IMWG and EBMT criteria
Measure:Progression-free survival (PFS)
Time Frame:every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
Safety Issue:
Description:Defined as the time from start of induction treatment to documented progressive disease (PD) or death from any cause up to 3 years post first study treatment
Measure:Overall survival (OS)
Time Frame:every 4 weeks until end of treatment visit, and up to 3 years thereafter
Safety Issue:
Description:Defined as the time from start of induction treatment to 3 years post first study treatment or death from any cause, whichever comes first
Measure:The number of treatment-emergent adverse events, serious adverse events, deaths as a measure of safety
Time Frame:weekly for 8 weeks, then every 2 weeks till start of mobilization and 70-120 days post-ASCT
Safety Issue:
Description:Safety data and abnormal lab values will be collected and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4.03) and abnormal vital signs.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:SCRI Development Innovations, LLC

Trial Keywords

  • B-cell tumors
  • autologous stem cell transplantation
  • blood cancers

Last Updated

September 13, 2019