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

NCT01478048 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CA204-0092011-002695-16
• Study Type: interventional
• Target: 185
• Locations: 5 countries
• Sites: 77

Brief Summary

The purpose of the study is to determine whether the addition of Elotuzumab to Bortezomib/ Dexamethasone will prolong the time before myeloma worsens \[progression free survival (PFS)\].

Conditions

Multiple Myeloma

Keywords

Relapsed/Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• 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

  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.

  Randomization until 111 events (disease progression or death), up to May 2014, approximately 2 years

• 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

  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.

  Randomization until 111 events, up to May 2014, approximately 2 years

• 1 Year Progression-Free Survival Rate - Randomized Participants

  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.

  Year 1 after last participant was randomized

Secondary Outcomes (3)

• 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

  Randomization until 111 events, up to May 2014, approximately 2 years

• Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants

  Randomization until 111 events, up to May 2014, approximately 2 years

• Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One FcγRIIIa V Allele

  Randomization until 111 events, up to May 2014, approximately 2 years

Study Arms (2)

Arm A: Elotuzumab + Bortezomib + Dexamethasone

EXPERIMENTAL

On days of Elotuzumab infusion: Dexamethasone (8mg IV + 8mg Oral) will be administered other days Dexamethasone 20 mg Oral will be administered

Biological: Elotuzumab; Drug: Bortezomib; Drug: Dexamethasone

Arm B: Bortezomib + Dexamethasone

ACTIVE COMPARATOR

Drug: Bortezomib; Drug: Dexamethasone

Interventions

Elotuzumab BIOLOGICAL

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

Also known as: BMS-901608

Arm A: Elotuzumab + Bortezomib + Dexamethasone

Bortezomib DRUG

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

Also known as: Velcade®

Arm A: Elotuzumab + Bortezomib + Dexamethasone; Arm B: Bortezomib + Dexamethasone

Dexamethasone DRUG

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

Also known as: Decadron®, Intensol®, Dexpak®, Taperpak®

Arm A: Elotuzumab + Bortezomib + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented progression from most recent line of therapy
• Measurable disease
• 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:
• The subject did not discontinue any proteasome inhibitor due to intolerance or grade ≥ 3 toxicity
• The subject is not refractory to any proteasome inhibitor, defined as progression during treatment or within 60 days after the last dose
• The subject previously achieved a partial response (PR) or better to previous proteasome inhibitor (PI)

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• AbbVie: collaborator

Study Sites (77)

Compassionate Cancer Res Grp

Corona, California, 92879, United States

Location

Local Institution

Corona, California, 92879, United States

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Local Institution

Long Beach, California, 90806, United States

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USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

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Ucla Department Of Medicine

Los Angeles, California, 90095, United States

Location

Medical Oncology Care Associates

Orange, California, 92868, United States

Location

Sharp Clinical Oncology Research

San Diego, California, 92123, United States

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Kaiser Permanente Medical Center

Vallejo, California, 94589, United States

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Local Institution

Vallejo, California, 94589, United States

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Cancer Specialists of North FL

Jacksonville, Florida, 32256, United States

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Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

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Palm Beach Cancer Institute

West Palm Beach, Florida, 33401, United States

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Kaiser Permanente-Moanalua Medical Center

Honolulu, Hawaii, 96819, United States

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University Of Chicago Medical Center

Chicago, Illinois, 60637, United States

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Local Institution

Decatur, Illinois, 62526, United States

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Oncology Specialists, S.C.

Park Ridge, Illinois, 60068, United States

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Local Institution

Urbana, Illinois, 61801, United States

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Investigative Clinical Research Of Indiana, Llc

Indianapolis, Indiana, 46260, United States

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Local Institution

Hazard, Kentucky, 41701, United States

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University Of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

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Pikeville Medical Center Leonard Lawson Cancer Center

Pikeville, Kentucky, 41501, United States

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Cancer Center Of Acadiana

Lafayette, Louisiana, 70503, United States

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Local Institution

Shreveport, Louisiana, 71101, United States

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Local Institution

Baltimore, Maryland, 21204, United States

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Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

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Local Institution

Worcester, Massachusetts, 01608, United States

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Henry Ford Health System

Detroit, Michigan, 48202, United States

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Mercy Medical Research Institute

Springfield, Missouri, 65807, United States

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Washington University School Of Medicine

St Louis, Missouri, 63110, United States

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Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

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Waverly Hematology Oncology

Cary, North Carolina, 27518, United States

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St. Agnes Hospital

Baltimore, Pennsylvania, 21229, United States

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Cancer Care Associates

Bethlehem, Pennsylvania, 18015, United States

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Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

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Penn State Hershey Cancer Inst

Hershey, Pennsylvania, 17033, United States

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The Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University Of South Carolina

Charleston, South Carolina, 29425, United States

Location

Local Institution

Greenville, South Carolina, 29615, United States

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Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

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Northwest Cancer Center

Houston, Texas, 77090, United States

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Fairfax, Virginia, 22031, United States

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Seattle, Washington, 98108, United States

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Grenoble, 38043, France

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Le Mans, 72037, France

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Lille, 59037, France

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Nantes, 44093, France

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Paris, 75012, France

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Toulouse, 31059, France

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Vandœuvre-lès-Nancy, 54500, France

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Milan, Parma, 20132, Italy

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Roma, Parma, 00144, Italy

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Ancona, 60126, Italy

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Bari, 70124, Italy

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Bologna, 40138, Italy

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Brescia, 25123, Italy

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Florence, 50134, Italy

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Genova, 16132, Italy

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Lecce, 73100, Italy

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Meldola (fc), 47014, Italy

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Modena, 41124, Italy

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Pescara, 65124, Italy

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Ravenna, 48100, Italy

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Rimini, 47900, Italy

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Roma, 00168, Italy

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Roma, 161, Italy

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Rome, 00144, Italy

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Torino, 10126, Italy

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Barcelona, 08003, Spain

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Madrid, 28006, Spain

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Murcia, 30008, Spain

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Salamanca, 37007, Spain

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Santiago Compostela, 15706, Spain

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Toledo, 45004, Spain

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Valencia, 46010, Spain

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Valencia, 46026, Spain

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Zaragoza, 50009, Spain

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Related Publications (1)

• Jakubowiak A, Offidani M, Pegourie B, De La Rubia J, Garderet L, Laribi K, Bosi A, Marasca R, Laubach J, Mohrbacher A, Carella AM, Singhal AK, Tsao LC, Lynch M, Bleickardt E, Jou YM, Robbins M, Palumbo A. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016 Jun 9;127(23):2833-40. doi: 10.1182/blood-2016-01-694604. Epub 2016 Apr 18.

  PMID: 27091875 DERIVED

Related Links

• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form

MeSH Terms

Conditions

Multiple Myeloma

Interventions

elotuzumab; Bortezomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2011
• First Posted: November 23, 2011
• Study Start: November 30, 2011
• Primary Completion: May 30, 2014
• Study Completion: April 21, 2017
• Last Updated: May 21, 2018
• Results First Posted: January 26, 2016

Record last verified: 2018-04

Locations

FR (7); IT (18); CA (1); ES (9); US (42)