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

Sponsor
SCRI Development Innovations, LLC (Other)
Overall Status
Completed
CT.gov ID
NCT02843074
Collaborator
Bristol-Myers Squibb (Industry)
55
Enrollment
6
Locations
1
Arm
60.5
Actual Duration (Months)
9.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
55 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 21, 2016
Actual Primary Completion Date :
Jul 27, 2021
Actual Study Completion Date :
Oct 5, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: ERd Therapy

INDUCTION: 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.

Drug: elotuzumab
Given intravenously (IV)
Other Names:
  • Empliciti
  • Drug: Lenalidomide
    Given by IV
    Other Names:
  • Revlimid
  • Drug: Dexamethasone
    Given orally (PO) or by IV
    Other Names:
  • Decadron
  • Procedure: autologous stem cell transplantation
    Other Names:
  • ASCT
  • Outcome Measures

    Primary Outcome Measures

    1. Induction Feasibility Rate (IFR) [weekly for 16 weeks]

      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

    1. Complete Response Rate (CRR) [every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years]

      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.

    2. Overall Response Rate (ORR) [every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years]

      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

    3. Progression-free survival (PFS) [every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years]

      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

    4. Overall survival (OS) [every 4 weeks until end of treatment visit, and up to 3 years thereafter]

      Defined as the time from start of induction treatment to 3 years post first study treatment or death from any cause, whichever comes first

    5. The number of treatment-emergent adverse events, serious adverse events, deaths as a measure of safety [weekly for 8 weeks, then every 2 weeks till start of mobilization and 70-120 days post-ASCT]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Colorado Blood Cancer InstituteDenverColoradoUnited States80218
    2Center for Cancer and Blood DisordersBethesdaMarylandUnited States20817
    3HCA Midwest Health/Research Medical CenterKansas CityMissouriUnited States64132
    4Nebraska Methodist HospitalOmahaNebraskaUnited States68114
    5Tennessee OncologyChattanoogaTennesseeUnited States37404
    6Tennessee OncologyNashvilleTennesseeUnited States37203

    Sponsors and Collaborators

    • SCRI Development Innovations, LLC
    • Bristol-Myers Squibb

    Investigators

    • Study Chair: Jesus Berdeja, MD, SCRI Development Innovations, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    SCRI Development Innovations, LLC
    ClinicalTrials.gov Identifier:
    NCT02843074
    Other Study ID Numbers:
    • SCRI MM61
    First Posted:
    Jul 25, 2016
    Last Update Posted:
    Oct 26, 2021
    Last Verified:
    Oct 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by SCRI Development Innovations, LLC
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 26, 2021