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

• Sponsor: Bristol-Myers Squibb
• Collaborator: AbbVie
• Information provided by (Responsible Party): Bristol-Myers Squibb

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Lenalidomide; Drug: Dexamethasone; Biological: Elotuzumab (BMS-901608)	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	90 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	January 22, 2015
Actual Primary Completion Date :	February 9, 2017
Estimated Study Completion Date :	December 31, 2020

Arms and Interventions

Arm	Intervention/treatment
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	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	Drug: Lenalidomide; Drug: Dexamethasone

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.

2. 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.
3. 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.

Eligibility Criteria

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Ages Eligible for Study:	20 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Locations

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Japan
Local Institution
Nagoya-shi, Aichi, Japan, 4600001
Local Institution
Nagoya-shi, Aichi, Japan, 4678602
Local Institution
Aomori-shi, Aomori, Japan, 0308553
Local Institution
Chiba-shi, Chiba, Japan, 2608677
Local Institution
Kamogawa-shi, Chiba, Japan, 2968602
Local Institution
Matsuyama-shi, Ehime, Japan, 7900024
Local Institution
Fukuoka-shi, Fukuoka, Japan, 8128582
Local Institution
Maebashi-shi, Gunma, Japan, 3718511
Local Institution
Shibukawa-shi, Gunma, Japan, 3770280
Local Institution
Fukuyama-shi, Hiroshima, Japan, 7200001
Local Institution
Kasama-shi, Ibaraki, Japan, 3091793
Local Institution
Morioka-shi, Iwate, Japan, 0208505
Local Institution
Kagoshima-shi, Kagoshima, Japan, 8920853
Local Institution
Kyoto-shi, Kyoto, Japan, 6028566
Local Institution
Sendai-shi, Miyagi, Japan, 9808574
Local Institution
Niigata-shi, Niigata, Japan, 9518566
Local Institution
Okayama-shi, Okayama, Japan, 7011192
Local Institution
Osaka-shi, Osaka, Japan, 5300012
Local Institution
Osaka-shi, Osaka, Japan, 5438555
Local Institution
Kawagoe-shi, Saitama, Japan, 3508550
Local Institution
Hamamatsu-shi, Shizuoka, Japan, 4313192
Local Institution
Utsunomiya-shi, Tochigi, Japan, 3200834
Local Institution
Bunkyo-ku, Tokyo, Japan, 1138677
Local Institution
Koto-ku, Tokyo, Japan, 1358550
Local Institution
Shibuya-ku, Tokyo, Japan, 1508935
Local Institution
Shinjuku-Ku, Tokyo, Japan, 1608582
Local Institution
Shinjuku-ku, Tokyo, Japan, 1628655
Local Institution
Tachikawa-shi, Tokyo, Japan, 1900014

Sponsors and Collaborators

Bristol-Myers Squibb

AbbVie

Investigators

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Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

  Study Documents (Full-Text)

Documents provided by Bristol-Myers Squibb:

Statistical Analysis Plan  [PDF] February 16, 2017

Study Protocol  [PDF] February 16, 2017

More Information

Additional Information:

FDA Safety Alerts and Recalls  BMS Clinical Trial Patient Recruiting  Investigator Inquiry Form 

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Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT02272803 History of Changes
Other Study ID Numbers:	CA204-116
First Posted:	October 23, 2014
Results First Posted:	March 22, 2018
Last Update Posted:	March 22, 2018
Last Verified:	February 2018

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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

Additional relevant MeSH terms:

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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	Dexamethasone acetate; Lenalidomide; Elotuzumab; 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