Elotuzumab, Lenalidomide and Dexamethasone in Treatment of Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: elotuzumab; Lenalidomide; Dexamethasone; autologous stem cell transplantation
Intervention description: Given intravenously (IV); Given by IV; Given orally (PO) or by IV
Intervention MeSH terms: Dexamethasone; Lenalidomide; Elotuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: B-cell tumors; autologous stem cell transplantation; blood cancers

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.
    

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.