A Phase 1b/2, Dose-Escalation Study of Elotuzumab (Humanized Anti-CS1 Monoclonal IgG1 Antibody) in Relapsed Multiple Myeloma

NCT00742560 | Completed Phase 2 Results DMC

• 2 other identifiers: HuLuc63-17032007-006677-83
• Study Type: interventional
• Target: 101
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Hematologic Cancer

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Lenalidomide and Dexamethasone (Phase 1)

  MTD was determined by testing increasing doses up to 20 mg/kg once daily dose escalation cohorts 1 to 3 with 3 patients each. MTD reflects highest dose of drug that did not cause an unacceptable side effect (dose limiting toxicity \[DLT\]) in more than 30% of patients; e.g., hematologic toxicities like Common Toxicity Criteria for Adverse Events (CTCAE) Grade 4 neutropenia in specific conditions, platelets \< 10,000 cells/mm\^3 that do not recover to 25,000 cells/mm\^3; and specific non-hematologic/biochemical toxicities CTCAE Grade 3 or 4 (except fatigue and Grade 3 infections); CTCAE version 3.0 were used.

  4 weeks

• Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 2)

  ORR: Percentage of participants with confirmed complete response (CR; negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and ≤5% plasma cells in bone marrow), partial response (PR; ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to ≤200 mg per 24 hour; if serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved free light chain (FLC\] levels is required in place of the M-protein criteria; if serum and urine M-protein are unmeasurable, and serum FLC is also unmeasurable, a ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%; and, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas), very good PR (VGPR; normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence), or stringent CR (sCR; CR plus VGPR).

  From date of randomization until 60 days following the last infusion (or before initiation of new therapy), up to 101 months

Secondary Outcomes (14)

• Objective Response Rate (ORR) According to the International Myeloma Working Group Uniform Response Criteria (Phase 1)

  From first dose of elotuzumab until 60 days following the last infusion (or before initiation of new therapy), up to 100.5 months

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  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)

• Number of Participants With Infusion Reactions

  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)

• Mean Serum Concentrations of Elotuzumab During Cycle 1

  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)

• Maximum Serum Concentration (Cmax) of Elotuzumab

  Cycle 1: Days 1, 8, and 15; Cycle 2: Days 1 and 22; Cycle 3 and beyond: Day 1

Study Arms (5)

Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

EXPERIMENTAL

Elotuzumab 5 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

Biological: elotuzumab; Drug: lenalidomide; Drug: dexamethasone oral; Drug: dexamethasone injection

Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

EXPERIMENTAL

Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

Biological: elotuzumab; Drug: lenalidomide; Drug: dexamethasone oral; Drug: dexamethasone injection

Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

EXPERIMENTAL

Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

Biological: elotuzumab; Drug: lenalidomide; Drug: dexamethasone oral; Drug: dexamethasone injection

Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2)

EXPERIMENTAL

Elotuzumab 10 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

Biological: elotuzumab; Drug: lenalidomide; Drug: dexamethasone oral; Drug: dexamethasone injection

Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2)

EXPERIMENTAL

Elotuzumab 20 mg/kg administered as an IV infusion in combination with lenalidomide 25 mg and dexamethasone 40 mg administered orally.

Biological: elotuzumab; Drug: lenalidomide; Drug: dexamethasone oral; Drug: dexamethasone injection

Interventions

elotuzumab BIOLOGICAL

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.

Also known as: HuLuc63

Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

lenalidomide DRUG

Lenalidomide 25 mg administered orally once daily on Days 1 to 21 of each 28-day cycle

Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

dexamethasone oral DRUG

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)

Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

dexamethasone injection DRUG

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)

Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 10 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 1); Elotuzumab 20 mg/kg + Lenalidomide and Dexamethasone (Phase 2); Elotuzumab 5 mg/kg + Lenalidomide and Dexamethasone (Phase 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older with a confirmed diagnosis of multiple myeloma (MM) and documentation of one to three prior therapies.
• Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior treatment.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Creatinine clearance ≥ 50 mL/min measured by Cockcroft-Gault method.
• 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.
• Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) \< 3 × upper limit of normal.
• Total bilirubin \< 2 × upper limit of normal, direct bilirubin \< 2.0 mg/dL.
• 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.
• 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).
• Able to take aspirin daily as prophylactic anticoagulation therapy (subjects intolerant to aspirin may use warfarin or low-molecular-weight heparin).

You may not qualify if:

• 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.
• 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).
• Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure.
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
• Treatment with any investigational drug within 2 weeks or 3 half lives (whichever is longer) of the first dose of elotuzumab.
• 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).
• Prior lenalidomide therapy.
• Prior peripheral stem-cell transplant within 12 weeks of the first dose of elotuzumab.
• Treatment with nitrosoureas, such as carmustine (BiCNU), nitrogen mustard agents, or melphalan, within 6 weeks of first dose of elotuzumab.
• Neuropathy ≥ Grade 3 or painful neuropathy ≥ Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v3.0).
• Known active infections requiring IV antibiotic, antiviral, or antifungal therapy.
• Hypersensitivity to recombinant proteins or excipients in elotuzumab, lenalidomide, or dexamethasone.
• Female subjects who are pregnant or breastfeeding.
• Subjects with serum calcium (corrected for albumin) ≥ 12 mg/dL.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Bristol-Myers Squibb: collaborator

Related Publications (1)

• 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.

  PMID: 26686406 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Multiple Myeloma

Interventions

elotuzumab; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

800-633-9110

Study Officials

• AbbVie Inc

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2008
• First Posted: August 27, 2008
• Study Start: August 1, 2008
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: January 10, 2018
• Results First Posted: January 10, 2018

Record last verified: 2018-01