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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01241292
First received: November 4, 2010
Last updated: January 22, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Multiple Myeloma
Biological: BMS-901608 (Elotuzumab) 10 mg
Biological: BMS-901608 (Elotuzumab) 20 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths [ Time Frame: First dose (Day 1) to last dose plus 60 days, up to 3 years ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Clinically Relevant Vital Sign Findings [ Time Frame: First dose (Day 1) to last dose plus 60 days, up to 3 years ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests [ Time Frame: First dose (Day 1) to last dose plus 60 days, up to 3 years ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests [ Time Frame: First dose (Day 1) to last dose plus 60 days, up to 3 years ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests [ Time Frame: First dose (Day 1) to last dose plus 60 days, up to 3 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Best Overall Response - Treated Participants [ Time Frame: Cycle 2 (Study Day 29) to last dose, up to 3 years ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 [ Time Frame: Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3 ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 [ Time Frame: Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants [ Time Frame: First dose (Day 1) to last dose plus 60 days, up to 3 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 7
Study Start Date: January 2011
Estimated Study Completion Date: August 2016
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241292

Locations
Japan
Local Institution
Nagoya-shi, Aichi, Japan, 4600001
Local Institution
Nagoya-shi, Aichi, Japan, 4678602
Local Institution
Niigata-shi, Niigata, Japan, 9518566
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01241292     History of Changes
Other Study ID Numbers: CA204-005 
Study First Received: November 4, 2010
Results First Received: December 16, 2015
Last Updated: January 22, 2016
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2016