Study of Bortezomib and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01478048
First received: November 2, 2011
Last updated: May 16, 2016
Last verified: January 2016
  Purpose
The purpose of the study is to determine whether the addition of Elotuzumab to Bortezomib/ Dexamethasone will prolong the time before myeloma worsens [progression free survival (PFS)].

Condition Intervention Phase
Multiple Myeloma
Biological: Elotuzumab
Drug: Bortezomib
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized Study of Bortezomib/Dexamethasone With or Without Elotuzumab in Subjects With Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Median Investigator-Assessed Progression-free Survival (PFS) Time (Months) From Randomization to Date of First Tumor Progression or Death Due to Any Cause - Randomized Participants [ Time Frame: Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years ] [ Designated as safety issue: No ]
    PE was planned for after at least 103 events; it was analyzed after 111 events. Response was assessed: Day 1 (± 7 days) of each cycle per modified International Myeloma Working Group (IMWG) criteria; assessed using adequate tumor assessment (ATA) (ie, serum and urine M-protein tests performed within 14 days of each other; imaging if baseline measurable extramedullary plasmacytoma existed). Progression: Any of following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/L); Bone marrow plasma cell percentage (≥10%). Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas. Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.

  • Number of Investigator-Assessed Progression-free Survival Events From Randomization to Date of First Tumor Progression or Death Due to Any Cause - All Randomized Participants [ Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years ] [ Designated as safety issue: No ]
    PE planned for after at least 103 events (progression/death); analyzed at 111 events. Those who neither progressed nor died were censored on the date of last adequate tumor assessment (ATA), which requires both serum and urine M-protein tests. If no post-baseline tumor assessments/no death, then censored on randomization day. Response assessed: Day 1 (± 7 days) each cycle; 30 and 60 days post treatment. Modified IMWG criteria used. Progression: Any of following: Increase of 25% in serum and/or urine M-component; if no measurable serum, urine M-protein levels, then difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/L) ; Bone marrow plasma cell percentage (≥10%). New bone lesions or soft tissue plasmacytomas or increase in size of existing lesions, plasmacytomas. Development of hypercalcemia attributed solely to plasma cell proliferative disorder. First dose occurs within 3 days of randomization.

  • 1 Year Progression-Free Survival Rate - Randomized Participants [ Time Frame: Year 1 after last participant was randomized ] [ Designated as safety issue: No ]
    PFS rate=Percentage probability of participants experiencing no progression or death up to 1 year, estimated using the Kaplan-Meier method. Response assessed by the investigator: Day 1 (± 7 days) of each cycle per modified IMWG criteria; assessed using ATA (ie, serum and urine M-protein tests performed within 14 days of each other; imaging done if baseline measurable extramedullary plasmacytoma existed). Progression: Any of the following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase > 100 mg/L) ; Bone marrow plasma cell percentage (≥10%). Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas. Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.


Secondary Outcome Measures:
  • Median Progression-free Survival Time (Months) From Randomization to Date of First Tumor Progression or Death Due to Any Cause, in Randomized Participants With at Least One FcγRIIIa V Allele [ Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years ] [ Designated as safety issue: No ]
    PE was planned for after at least 103 events; it was analyzed after 111 events. Response was assessed: Day 1 (± 7 days) of each cycle per modified IMWG criteria; assessed using adequate tumor assessment (ATA) (ie, serum and urine M-protein tests performed within 14 days of each other; imaging if baseline measurable extramedullary plasmacytoma existed). Progression: Any of following: Increase of 25% from lowest response in 1 or more: serum and/or urine M-component; in those without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase > 100 mg/L); Bone marrow plasma cell percentage (≥10%). Definite new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing lesions or plasmacytomas. Development of hypercalcemia attributed solely to the plasma cell proliferative disorder. Randomized participants with at least 1 FcγRIIIa V allele were a sub-set of all randomized participants.

  • Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants [ Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years ] [ Designated as safety issue: No ]
    ORR was calculated for participants with a best overall response (BOR) of partial response (PR) or better, including stringent complete response (sCR), complete response (CR), and very good partial response (VGPR). BOR was determined by the investigator based on myeloma tumor assessments using IMWG criteria: CR=Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal FLC ratio and absence of clonal cells in bone marrow; VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hour; PR= ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hour. ORR= number of participants responding divided by total number of participants randomized, measured as a percentage.

  • Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One FcγRIIIa V Allele [ Time Frame: Randomization until 111 events, up to May 2014, approximately 2 years ] [ Designated as safety issue: No ]
    ORR was calculated for participants with a BOR of PR or better, sCR, CR, and VGPR. BOR was determined by the investigator based on myeloma tumor assessments using IMWG criteria: CR=Negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow; sCR= CR + normal FLC ratio and absence of clonal cells in bone marrow; VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein level + urine M-protein level < 100 mg per 24 hour; PR= ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hour. ORR= number of participants responding divided by total number of participants randomized, measured as a percentage. Randomized participants with at least 1 FcγRIIIa V allele were a sub-set of all randomized participants.


Enrollment: 185
Study Start Date: November 2011
Estimated Study Completion Date: August 2016
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Elotuzumab + Bortezomib + Dexamethasone
On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered
Biological: Elotuzumab
Solution; Intravenous (IV); 10 mg/kg; (Cycles 1 & 2: Days 1, 8 & 15; Cycles 3-8: Days 1 & 11; Cycle 9+: Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Name: BMS-901608
Drug: Bortezomib
Solution; IV; 1.3 mg/m2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until subject meets criteria for discontinuation of study drug
Other Name: Velcade®
Drug: Dexamethasone
Tablets; Oral; 20 mg; (Cycles 1& 2: once daily on Days 2, 4, 5, 8, 9, 11; Cycles 3-8: once daily on Days 2, 4, 5, 9, 12; Cycles 9+: once daily on Days 2, 8, 9, 16); Until subject meets criteria for discontinuation of study drug
Other Names:
  • Decadron®
  • Intensol®
  • Dexpak®
  • Taperpak®
Drug: Dexamethasone
Tablets; Oral; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
  • Decadron®
  • Intensol®
  • Dexpak®
  • Taperpak®
Drug: Dexamethasone
Solution; IV; 8 mg; (Cycles 1& 2: Days 1, 8, 15; Cycles 3-8: Days 1 &11; Cycles 9+; Days 1 & 15); Until subject meets criteria for discontinuation of study drug
Other Names:
  • Decadron®
  • Intensol®
  • Dexpak®
  • Taperpak®
Active Comparator: Arm B: Bortezomib + Dexamethasone Drug: Bortezomib
Solution; IV; 1.3 mg/m2; (Cycles 1 - 8: Days 1, 4, 8, 11; Cycles 9+: Days 1, 8, 15); Until subject meets criteria for discontinuation of study drug
Other Name: Velcade®
Drug: Dexamethasone
Tablets; Oral; 20 mg; (Cycles 1-8 once daily on Days 1, 2, 4, 5, 8, 9, 11, 12; Cycles 9+ once daily on Days 1, 2, 8, 9, 15, 16); Until subject meets criteria for discontinuation of study drug
Other Names:
  • Decadron®
  • Intensol®
  • Dexpak®
  • Taperpak®

  Eligibility

Ages Eligible for Study:   18 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:

  • Documented progression from most recent line of therapy
  • Measurable disease
  • 1 to 3 prior lines of therapy

    • Subjects may be proteasome inhibitor naive or have received prior proteasome inhibitor therapy provided all the following criteria are met:

      1. The subject did not discontinue any proteasome inhibitor due to intolerance or grade ≥ 3 toxicity
      2. The subject is not refractory to any proteasome inhibitor, defined as progression during treatment or within 60 days after the last dose
      3. The subject previously achieved a partial response (PR) or better to previous proteasome inhibitor (PI)

Exclusion Criteria:

  • Monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, or Waldenstrom's macroglobulinemia
  • Active plasma cell leukemia
  • Known Human immunodeficiency virus (HIV) infection or active hepatitis A, B, or C
  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: NCT01478048

  Hide Study Locations
Locations
United States, California
Compassionate Cancer Care Medical Group Inc
Corona, California, United States, 92879
Local Institution
Corona, California, United States, 92879
Local Institution
Long Beach, California, United States, 90806
Usc Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Ucla Department Of Medicine
Los Angeles, California, United States, 90095
Medical Oncology Care Associates
Orange, California, United States, 92868
Sharp Clinical Oncology Research
San Diego, California, United States, 92123
Kaiser Permanente Medical Center
Vallejo, California, United States, 94589
Local Institution
Vallejo, California, United States, 94589
United States, Florida
Cancer Specialists Of North Florida Beaches
Jacksonville, Florida, United States, 32256
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Hawaii
Kaiser Permanente-Moanalua Medical Center
Honolulu, Hawaii, United States, 96819
United States, Illinois
University Of Chicago Medical Center
Chicago, Illinois, United States, 60637
Local Institution
Decatur, Illinois, United States, 62526
Oncology Specialists, S.C.
Park Ridge, Illinois, United States, 60068
Local Institution
Urbana, Illinois, United States, 61801
United States, Indiana
Investigative Clinical Research Of Indiana, Llc
Indianapolis, Indiana, United States, 46260
United States, Kentucky
Local Institution
Hazard, Kentucky, United States, 41701
University Of Kentucky Markey Cancer Center
Lexington, Kentucky, United States, 40536
Pikeville Medical Center
Pikeville, Kentucky, United States, 41501
United States, Louisiana
Cancer Center Of Acadiana
Lafayette, Louisiana, United States, 70503
Local Institution
Shreveport, Louisiana, United States, 71101
United States, Maryland
Local Institution
Baltimore, Maryland, United States, 21204
United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02215
Local Institution
Worcester, Massachusetts, United States, 01608
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University School Of Medicine
Saint Louis, Missouri, United States, 63110
Mercy Medical Research Institute
Springfield, Missouri, United States, 65807
United States, Nevada
Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
United States, North Carolina
Waverly Hematology Oncology
Cary, North Carolina, United States, 27518
United States, Pennsylvania
St. Agnes Hospital
Baltimore, Pennsylvania, United States, 21229
Cancer Care Associates
Bethlehem, Pennsylvania, United States, 18015
Penn State Hershey Cancer Institute
Hershey, Pennsylvania, United States, 17033
Penn State Hershey Cancer Inst
Hershey, Pennsylvania, United States, 17033
The Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Medical University Of South Carolina
Charleston, South Carolina, United States, 29425
Local Institution
Greenville, South Carolina, United States, 29615
United States, Texas
Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
Northwest Cancer Center
Houston, Texas, United States, 77090
United States, Virginia
Local Institution
Fairfax, Virginia, United States, 22031
United States, Washington
Local Institution
Seattle, Washington, United States, 98108
Canada, Nova Scotia
Local Institution
Halifax, Nova Scotia, Canada, B3H 2Y9
France
Local Institution
Grenoble Cedex 9, France, 38043
Local Institution
Le Mans, France, 72037
Local Institution
Lille Cedex, France, 59037
Local Institution
Nantes, France, 44093
Local Institution
Paris 12, France, 75012
Local Institution
Toulouse, France, 31059
Local Institution
Vandoeuvre Les Nancy, France, 54500
Italy
Local Institution
Milano, Parma, Italy, 20132
Local Institution
Roma, Parma, Italy, 00144
Local Institution
Ancona, Italy, 60126
Local Institution
Bari, Italy, 70124
Local Institution
Bologna, Italy, 40138
Local Institution
Brescia, Italy, 25123
Local Institution
Firenze, Italy, 50134
Local Institution
Genova, Italy, 16132
Local Institution
Lecce, Italy, 73100
Local Institution
Modena, Italy, 41124
Local Institution
Pescara, Italy, 65124
Local Institution
Ravenna, Italy, 48121
Local Institution
Rimini, Italy, 47014
Local Institution
Rimini, Italy, 47900
Local Institution
Roma, Italy, 00168
Local Institution
Roma, Italy, 161
Local Institution
Rome, Italy, 00144
Local Institution
Torino, Italy, 10126
Spain
Local Institution
Barcelona, Spain, 08003
Local Institution
Madrid, Spain, 28006
Local Institution
Murcia, Spain, 30008
Local Institution
Salamanca, Spain, 37007
Local Institution
Santiago Compostela, Spain, 15706
Local Institution
Toledo, Spain, 45004
Local Institution
Valencia, Spain, 46010
Local Institution
Valencia, Spain, 46026
Local Institution
Zaragoza, Spain, 50009
Sponsors and Collaborators
Bristol-Myers Squibb
AbbVie
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01478048     History of Changes
Other Study ID Numbers: CA204-009  2011-002695-16 
Study First Received: November 2, 2011
Results First Received: December 17, 2015
Last Updated: May 16, 2016
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
Spain: Spanish Agency of Medicines

Keywords provided by Bristol-Myers Squibb:
Relapsed/Refractory Multiple Myeloma

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
Bortezomib
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 25, 2016