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
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.
- Newly diagnosed myeloma requiring systemic chemotherapy as per International Myeloma
Working Group (IMWG) uniform criteria and Diagnostic Criteria and Staging for Multiple
- 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
- 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.
- Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes
- 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
- 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.