Clinical trial NCT00742560: A Phase 1b/2, Dose-Escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Relapsed Multiple Myeloma
Official title: A Phase 1b/2, Multicenter, Open-label, Dose-escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Combination With Lenalidomide and Dexamethasone in Subjects With Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematologic Cancer
Keywords: Multiple Myeloma
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2008-08-27
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Lenalidomide and Dexamethasone (Phase 1)
timeFrame: 4 weeks
measure: Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 2)
timeFrame: From date of randomization until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
Secondary outcomes:
measure: Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 1)
timeFrame: From first dose of elotuzumab until 60 days following the last infusion (or before initiation of new therapy), up to 100.5 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 60 days after the last dose of study drug (up to 95 months)
measure: Number of Participants With Infusion Reactions
timeFrame: Cycles 1 and 2: Days 1, 8, 15, and 22 (day of infusion of elotuzumab) and Days 2, 9, 16, and 23 (day following infusion); and Cycles 3 and greater: Days 1 and 15 (day of infusion) and Days 2 and 16 (day after infusion) (up to 95 months)
measure: Mean Serum Concentrations of Elotuzumab During Cycle 1
timeFrame: Cycle 1: Days 1 (pre-infusion and 0.5, 2 and 4 hours post-infusion), 8 (pre-infusion and 0.5 and 2 hours post-infusion), 15 (pre-infusion and 0.5 hours and 2 hours post-infusion), and 22 (pre-infusion and 0.5, 2, and 4 hours post-infusion)
measure: Maximum Serum Concentration (Cmax) of Elotuzumab
timeFrame: Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1
measure: Area Under the Concentration-time Curve From 0 to Infinity (AUC0-inf) of Elotuzumab
timeFrame: Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1
measure: Systemic Clearance (CL) of Elotuzumab
timeFrame: Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1
measure: Volume of Distribution (V) of Elotuzumab
timeFrame: Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1
measure: Serum Half-life (t1/2) of Elotuzumab
timeFrame: Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1
measure: Duration of Response
timeFrame: From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
measure: Time to Progression (TTP)
timeFrame: From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
measure: Progression-free Survival (PFS)
timeFrame: From first dose of elotuzumab (phase 1) or randomization (phase 2) until 60 days following the last infusion (or before initiation of new therapy), up to 101 months
measure: Percentage of Participants With Treatment-emergent Anti-elotuzumab Antibody (ADA)
timeFrame: From screening through 60-day follow up period (up to 101 months)
measure: Plasma Cell Myeloma Cytogenetic Subtype
timeFrame: Screening (up to 14 days prior to dosing)
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc
role: STUDY_DIRECTOR
References:
citation: Richardson PG, Jagannath S, Moreau P, Jakubowiak AJ, Raab MS, Facon T, Vij R, White D, Reece DE, Benboubker L, Zonder J, Tsao LC, Anderson KC, Bleickardt E, Singhal AK, Lonial S; 1703 study investigators. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study. Lancet Haematol. 2015 Dec;2(12):e516-27. doi: 10.1016/S2352-3026(15)00197-0. Epub 2015 Nov 16.