Clinical trial NCT02843074: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: B-cell tumors
autologous stem cell transplantation
blood cancers
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2016-07-25
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Induction Feasibility Rate (IFR)
timeFrame: approximately 22 weeks (16 weeks of treatment and 6 weeks allowance for planning and scheduling mobilization and ASCT).
Secondary outcomes:
measure: Complete Response Rate (CRR) for Complete Time on Study
timeFrame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
measure: Overall Response Rate (ORR) for Complete Time on Study
timeFrame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
measure: Progression-free Survival (PFS)
timeFrame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years
measure: Overall Survival (OS)
timeFrame: every 4 weeks until end of treatment visit, and up to 3 years thereafter
measure: Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety
timeFrame: weekly for 8 weeks, then every 2 weeks till the start of mobilization for Induction and 70-120 days post-ASCT, every 2 weeks during 16 weeks of Consolidation, and monthly for 24 months of Maintenance, up to 30 days after last dose of study drugs.
measure: Consolidation Feasibility Rate (CFR)
timeFrame: approximately 55 weeks (16 weeks of induction treatment, 6 weeks allowance for planning and scheduling mobilization and ASCT, 17 weeks pause in treatment after ASCT, 16 weeks of consolidation treatment).
measure: Maintenance Feasibility Rate (MFR)
timeFrame: approximately 159 weeks (16 weeks of induction treatment, 6 weeks allowance for planning and scheduling mobilization and ASCT, 17 weeks pause in treatment after ASCT, 16 weeks of consolidation treatment, 104 weeks/2 years of maintenance treatment)
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Kansas City
country: United States
facility: HCA Midwest Health/Research Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
affiliation: SCRI Development Innovations, LLC
name: Jesus Berdeja, MD
role: STUDY_CHAIR
References: