A Phase 1b/2, Dose-Escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Relapsed Multiple Myeloma
Condition: Hematologic Cancer
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Neoplasms
Intervention: elotuzumab; lenalidomide; dexamethasone oral; dexamethasone injection
Intervention description: Humanized Anti-CS1 Monoclonal IgG1 Antibody (HuLuc63) administered as an intravenous infusion once a week during Cycles 1 and 2, and every other week beginning with Cycle 3.; Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle; Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously); Dexamethasone 40 mg administered orally once weekly; during weeks when elotuzumab is also administered, dexamethasone was administered as a split dose (28 mg orally and 8 mg intravenously)
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Lenalidomide; Elotuzumab; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma

Summary:

      The purpose of this study is to evaluate the combination of elotuzumab, lenalidomide, and
      dexamethasone in subjects with relapsed multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 years or older with a confirmed diagnosis of multiple myeloma (MM) and
             documentation of one to three prior therapies.

          2. Confirmed evidence of disease progression from immediately prior MM therapy or
             refractory to the immediately prior treatment.

          3. Measurable monoclonal (M-) protein component in serum (≥ 0.5 g/dL) and/or urine (if
             present), (≥ 0.2 g excreted in a 24 hour collection sample). Subjects with free light
             chain only disease are excluded.

          4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

          5. Creatinine clearance ≥ 50 mL/min measured by Cockcroft-Gault method.

          6. Hematologic parameters defined by:

               -  Absolute neutrophil count >1000 cells/mm^3 without growth factors for 7 days.

               -  Platelets ≥ 75,000 cells/mm^3 (75 × 10^9/L), without platelet transfusion, within
                  72 hours of screening evaluation.

               -  Hemoglobin ≥ 8 g/dL without red blood cell transfusion within 72 hours of
                  screening.

          7. Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) < 3 × upper limit
             of normal.

          8. Total bilirubin < 2 × upper limit of normal, direct bilirubin < 2.0 mg/dL.

          9. Negative urine pregnancy test in women of childbearing potential at screening and
             prior to prescribing lenalidomide. Females of childbearing potential (FCBP) must
             either commit to continued abstinence from heterosexual intercourse or begin
             acceptable methods of birth control for 28 days prior to prescribing lenalidomide. Men
             must agree to use a latex condom during sexual contact with FCBP even if they have had
             a successful vasectomy, and must agree not to donate semen during study drug therapy
             and for a period of time after therapy.

         10. Able to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information (in accordance
             with national and local subject's privacy regulations).

         11. Able to take aspirin daily as prophylactic anticoagulation therapy (subjects
             intolerant to aspirin may use warfarin or low-molecular-weight heparin).

        Exclusion Criteria:

          1. Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in-situ cervical cancer, or other cancer from which the subject has been
             disease-free for at least 2 years.

          2. Active or prior plasma cell leukemia (defined as either 20% of peripheral WBC
             comprised of plasma/CD138+ cells or an absolute count of 2 x 10^9/L).

          3. Uncontrolled medical problems such as diabetes mellitus, coronary artery disease,
             hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart
             failure.

          4. Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma
             cell dyscrasia.

          5. Treatment with any investigational drug within 2 weeks or 3 half lives (whichever is
             longer) of the first dose of elotuzumab.

          6. Use of corticosteroids, thalidomide, bortezomib, or cytotoxic chemotherapy within 2
             weeks of the first dose of elotuzumab except for steroids with little or no systemic
             absorption (ie, topical or inhaled steroids).

          7. Prior lenalidomide therapy.

          8. Prior peripheral stem-cell transplant within 12 weeks of the first dose of elotuzumab.

          9. Treatment with nitrosoureas, such as carmustine (BiCNU), nitrogen mustard agents, or
             melphalan, within 6 weeks of first dose of elotuzumab.

         10. Neuropathy ≥ Grade 3 or painful neuropathy ≥ Grade 2 (National Cancer Institute Common
             Terminology Criteria for Adverse Events [NCI CTCAE] v3.0).

         11. Known active infections requiring IV antibiotic, antiviral, or antifungal therapy.

         12. Hypersensitivity to recombinant proteins or excipients in elotuzumab, lenalidomide, or
             dexamethasone.

         13. Female subjects who are pregnant or breastfeeding.

         14. Subjects with serum calcium (corrected for albumin) ≥ 12 mg/dL.