Phase II Study of Lenalidomide/Dexamethasone With or Without Elotuzumab for Newly Diagnosed MM Patients in Japan

• ClinicalTrials.gov Identifier: NCT02272803
• Recruitment Status: Active, not recruiting
• First Posted: October 23, 2014
• Results First Posted: March 22, 2018
• Last Update Posted: June 4, 2020
• Sponsor: Bristol-Myers Squibb
• Collaborator: AbbVie
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: October 21, 2014
• First Posted Date: October 23, 2014
• Results First Submitted Date: January 26, 2018
• Results First Posted Date: March 22, 2018
• Last Update Posted Date: June 4, 2020
• Actual Study Start Date: January 22, 2015
• Actual Primary Completion Date: February 9, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 22, 2018)

Objective Response Rate (ORR) of Participants Treated With Elotuzumab + Lenalidomide/Dexamethasone (E-Ld) [ Time Frame: From first dose until documented response (assessed up to February 2017, approximately 24 months) ]

ORR is the proportion of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or PR as determined by investigator using the International Myeloma Working Group (IMWG) response criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

• Original Primary Outcome Measures (submitted: October 21, 2014): Objective Response Rate (ORR) - The percentage of patients who have a partial or better response to Lenalidomide/Dexamethasone + Elotuzumab therapy [ Time Frame: Approximately 24 months ]

Current Secondary Outcome Measures (submitted: February 22, 2018)

• Objective Response Rate (ORR) in All Treated Participants [ Time Frame: From first dose until documented response (assessed up to February 2017, approximately 24 months) ]
  ORR is the proportion of randomized participants who achieve a stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or PR as determined by investigator using the International Myeloma Working Group (IMWG) response criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
• Progression Free Survival (PFS) in Lenalidomide/Dexamethasone + Elotuzumab and Lenalidomide/Dexamethasone Therapy [ Time Frame: From randomization to the date of first documented tumor progression or death due to any cause (assessed up to February 2017, approximately 24 months) ]
  PFS was defined as the time from randomization to the date of the first documented tumor progression, as determined by the investigator using the IMWG response criteria, or to death due to any cause, provided death does not occur more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical deterioration will not be considered progression.
• PFS Rate at 1 Year [ Time Frame: 1 year ]
  The number of participants with PFS at 1 year post-randomization was divided by the total number randomized in that arm and expressed as a percentage. PFS was defined as the time from randomization to the date of the first documented tumor progression, as determined by the investigator using the IMWG response criteria, or to death due to any cause, provided death does not occur more than 10 weeks (2 or more assessment visits) after the last tumor assessment. Clinical deterioration will not be considered progression.

• Original Secondary Outcome Measures (submitted: October 21, 2014): The difference in ORR between Lenalidomide/Dexamethasone + Elotuzumab and Lenalidomide/Dexamethasone therapy [ Time Frame: Approximately 24 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II Study of Lenalidomide/Dexamethasone With or Without Elotuzumab for Newly Diagnosed MM Patients in Japan
• Official Title: A Phase 2, Randomized, Open Label Trial of Lenalidomide/Dexamethasone With or Without Elotuzumab in Subjects With Previously Untreated Multiple Myeloma in Japan
• Brief Summary: The purpose of this study is to determine the efficacy of Lenalidomide/Dexamethasone + Elotuzumab in the subjects with newly diagnosed, previously untreated Multiple Myeloma (MM) in Japan.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Lenalidomide
• Drug: Dexamethasone
• Biological: Elotuzumab (BMS-901608)

Study Arms

• Experimental: Arm A: Lenalidomide + Dexamethasone + Elotuzumab (BMS-901608)

  Drug: Lenalidomide

  Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Drug: Dexamethasone

  Tablets, Oral 28 mg and Intravenous (IV) 8 mg, once daily, on Days 1, 8, 15, 22 (cycles 1&2) ; Days 1 &15 (cycles 3-18); Day 1 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Tablets, Oral, 40 mg, once daily, on Days 8 & 22 (cycles 3-18); Days 8, 15, 22 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Biological: Elotuzumab (BMS-901608)

  Solution, Intravenous (IV), 10 mg/kg, weekly, on Days 1, 8, 15, 22 (cycles 1&2); Days 1 and 15 (cycles 3-18), Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Solution, Intravenous (IV), 20 mg/kg, Day 1 (cycle 19 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Interventions:

  • Drug: Lenalidomide
  • Drug: Dexamethasone
  • Biological: Elotuzumab (BMS-901608)
• Active Comparator: Arm B: Lenalidomide + Dexamethasone

  Drug: Lenalidomide

  Capsules, Oral, 25 mg, once daily, on Days 1-21, Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Drug: Dexamethasone

  Tablets, Oral, 40 mg, weekly, on Days 1, 8, 15, 22, Repeat every 28 days until subject meets criteria for discontinuation of study drug

  Interventions:

  • Drug: Lenalidomide
  • Drug: Dexamethasone

• Publications *: Suzuki A, Kakugawa S, Miyoshi M, Hori M, Suzuki K, Furukawa Y, Ohta K. Soluble SLAMF7 is a predictive biomarker for elotuzumab therapy. Leukemia. 2020 Nov;34(11):3088-3090. doi: 10.1038/s41375-020-0860-7. Epub 2020 May 12.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 17, 2017): 90
• Original Estimated Enrollment (submitted: October 21, 2014): 80
• Estimated Study Completion Date: December 31, 2020
• Actual Primary Completion Date: February 9, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Newly diagnosed with symptomatic Multiple Myeloma (MM)
• Have not received any prior systemic anti-myeloma therapy
• Have measurable disease
• Are not candidates for high-dose therapy plus stem-cell transplantation (SCT) because of age (≥ 65 years) or coexisting conditions. Refusal to undergo high dose therapy with SCT is NOT sufficient for entry onto CA204-116 for a subject < 65 years old. There must be a comorbidity that prevents SCT for a subject < 65 years old

Exclusion Criteria:

• Non-secretory myeloma
• Smoldering MM, defined as asymptomatic MM with absence of lytic bone lesions
• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Active plasma cell leukemia
• Known Human Immunodeficiency Virus (HIV) infection or active hepatitis A, B, or C

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT02272803
• Other Study ID Numbers: CA204-116
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: AbbVie

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: June 2020