Japanese Study of BMS-901608 (Elotuzumab) in Combination With Lenalidomide and Low Dose Dexamethasone

Phase 1 Multiple Ascending Dose Study of Elotuzumab (BMS-901608) in Combination With Lenalidomide/Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma in Japan

The purpose of this study is to assess the safety and tolerability of Elotuzumab when given in combination with Lenalidomide and low-dose Dexamethasone in subjects with relapsed or refractory multiple myeloma (MM) in Japan.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: BMS-901608 (Elotuzumab) 10 mg; Biological: BMS-901608 (Elotuzumab) 20 mg

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4600001
      • Local Institution
    • Nagoya-shi, Aichi, Japan, 4678602
      • Local Institution
  • Niigata
    • Niigata-shi, Niigata, Japan, 9518566
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

Inclusion Criteria:

• Received between 1 to 4 prior lines of therapy
• Measureable disease
• Men and women of childbearing potential (WOCBP) must be using two acceptable methods of contraception
• Men must agree to use a latex condom and a second form of birth control during sexual contact with WOCBP and must agree to not donate semen during study drug therapy
• Subjects must be willing to refrain from blood donations during study drug therapy

Exclusion Criteria:

• Subjects with non-secretory or oligo-secretory or light-chain only myeloma or active/prior plasma cell leukemia or known /suspect POEMS syndrome
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
• Unable to take aspirin daily as prophylactic anticoagulation therapy. Prior history of inability to tolerate weekly 40 mg dexamethasone
• History of renal failure
• History of clinical significant thrombosis, such as treatment for thrombosis was required

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-901608 (Elotuzumab) 10mg	Biological: BMS-901608 (Elotuzumab) 10 mg; Injection, Intravenous, 10 mg/kg, Weekly at cycle 1 and 2, bi-weekly at cycle 3 and thereafter, Until disease progression or unacceptable toxicity became apparent
Experimental: BMS-901608 (Elotuzumab) 20mg	Biological: BMS-901608 (Elotuzumab) 20 mg; Injection, Intravenous, 20 mg/kg, Weekly at cycle 1 and 2, bi-weekly at cycle 3 and thereafter, Until disease progression or unacceptable toxicity became apparent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Data cut-off February 2014.	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Number of Participants With Clinically Relevant Vital Sign Findings	Vital signs (body temperature, seated blood pressure, heart rate, and respiration rate) were recorded at screening on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycle 3, and at the end of treatment. Blood pressure (Diastolic and Systolic) and heart rate were recorded after the participant sat quietly for at least 5 minutes. Clinical relevance of vital sign data was determined by the investigator.	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Lymphocytes (absolute) Gr 1: <1.5 to 0.8 *10^3 c/µL, Gr 2 <0.8 to 0.5 *10^3 c/µL, Gr 3: <0.5 to 0.2 *10^3 c/µL, Gr 4: <0.2*10^3 c/µL. Neutrophils (absolute): Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Leukocytes Gr 1:<LLN to 3.0 *10^3 c/µL, Gr 2; <3.0 to 2.0 *10^3 c/µL, Gr 3: <2.0 to 1.0 *10^3 c/µL, Gr 4: <1.0 *10^3 c/µL.	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN to 3 grams per deciliter (g/dL); Gr 2: <3.0 - 2.0 g/L; Gr 3: < 2 g/dL. Creatinine Gr 1: >1 - 1.5*baseline (BL)to >ULN - 1.5*ULN; Gr 2: >1.5 - 3.0*BL to > 1.5 - 3.0*ULN; Gr 3: >3.0*BL to > 3.0 - 6.0*ULN; Gr 4: >6.0*ULN.	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests	NCI CTCAE, version 3.0 was used to measure toxicity scale. Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:<LLN - 130; Gr 3: <130 - 120; Gr 4: <120 mmol/L. Potassium (H) Gr 1: >ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1 - Gr 2: <LLN - 3.0; Gr 3: < 3.0 - 2.5; Gr 4: <2.5 mmol/L.	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Best Overall Response - Treated Participants	Complete response (CR) and Partial Response (PR) were based on the European Group for Blood and Bone Marrow Transplant (EBMT) Criteria. Very Good Partial response was derived from the International Myeloma Working Group (IMWG) criteria. Participants who had a reduction in M-protein or plasmacytoma but did not meet the EBMT criteria for PR were classified as minimal response (MR). Hematologic, radiologic and/or clinical assessments were done every cycle starting with cycle 2. Each cycle is 4 weeks in length (Day 1, Day 8, Day 15, Day 22). Cycle 2 began on study Day 29. CR=negative immunofixation 6 weeks, <5% plasma cells, no increase in size or number of lytic lesions, complete disappearance of extramedullary plasmacytoma. PR=≥50%reduction in M-protein for 6 weeks, ≥90% reduction of urinary light chain excretion or < 200 mg/24hours for 6 weeks, ≥50% reduction in size of extramedullary plasmacytoma present at baseline, no increase in size or number of lytic lesions.	Cycle 2 (Study Day 29) to last dose (assessed up to January 2017, approximately 71 months)
Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3	The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.	Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3
Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3	The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmin was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.	Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3
Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants	The detection of anti-elotuzumab anti-drug antibodies (ADAs) in human serum was performed using a validated bridging electrochemiluminescence immunoassay (ECLA) on the Meso Scale Discovery (MSD) platform. Sample collection was performed prior to administration of elotuzumab at Day 1 of each cycle.	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Iida S, Nagai H, Kinoshita G, Miyoshi M, Robbins M, Pandya D, Bleickardt E, Chou T. Elotuzumab with lenalidomide and dexamethasone for Japanese patients with relapsed/refractory multiple myeloma: phase 1 study. Int J Hematol. 2017 Mar;105(3):326-334. doi: 10.1007/s12185-016-2138-4. Epub 2016 Nov 15.

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2011
• Primary Completion (Actual): February 14, 2014
• Study Completion (Actual): January 16, 2017

Study Registration Dates

• First Submitted: November 4, 2010
• First Submitted That Met QC Criteria: November 12, 2010
• First Posted (Estimate): November 16, 2010

Study Record Updates

• Last Update Posted (Actual): February 15, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Elotuzumab
• Other Study ID Numbers: CA204-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes