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

Multiple Myeloma Clinical Trial

Official title:

A Phase 2, Randomized Study of Bortezomib/Dexamethasone With or Without Elotuzumab in Subjects With Relapsed/Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01478048
• Other study ID #: CA204-009
• Secondary ID: 2011-002695-16
• Status: Completed
• Phase: Phase 2
• Start date: November 30, 2011
• Est. completion date: April 21, 2017

Study information

• Verified date: April 2018
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: April 21, 2017
• Est. primary completion date: May 30, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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

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
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
Canada	Local Institution	Halifax	Nova Scotia
France	Local Institution	Grenoble Cedex 9
France	Local Institution	Le Mans
France	Local Institution	Lille Cedex
France	Local Institution	Nantes
France	Local Institution	Paris 12
France	Local Institution	Toulouse
France	Local Institution	Vandoeuvre Les Nancy
Italy	Local Institution	Ancona
Italy	Local Institution	Bari
Italy	Local Institution	Bologna
Italy	Local Institution	Brescia
Italy	Local Institution	Firenze
Italy	Local Institution	Genova
Italy	Local Institution	Lecce
Italy	Local Institution	Meldola (fc)
Italy	Local Institution	Milano	Parma
Italy	Local Institution	Modena
Italy	Local Institution	Pescara
Italy	Local Institution	Ravenna
Italy	Local Institution	Rimini
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Italy	Local Institution	Roma	Parma
Italy	Local Institution	Rome
Italy	Local Institution	Torino
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Murcia
Spain	Local Institution	Salamanca
Spain	Local Institution	Santiago Compostela
Spain	Local Institution	Toledo
Spain	Local Institution	Valencia
Spain	Local Institution	Valencia
Spain	Local Institution	Zaragoza
United States	Local Institution	Baltimore	Maryland
United States	St. Agnes Hospital	Baltimore	Pennsylvania
United States	Cancer Care Associates	Bethlehem	Pennsylvania
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Waverly Hematology Oncology	Cary	North Carolina
United States	Medical University Of South Carolina	Charleston	South Carolina
United States	University Of Chicago Medical Center	Chicago	Illinois
United States	Compassionate Cancer Res Grp	Corona	California
United States	Local Institution	Corona	California
United States	Charles A. Sammons Cancer Center	Dallas	Texas
United States	Local Institution	Decatur	Illinois
United States	Henry Ford Health System	Detroit	Michigan
United States	Local Institution	Fairfax	Virginia
United States	Local Institution	Greenville	South Carolina
United States	Local Institution	Hazard	Kentucky
United States	Penn State Hershey Cancer Inst	Hershey	Pennsylvania
United States	Penn State Hershey Cancer Institute	Hershey	Pennsylvania
United States	Kaiser Permanente-Moanalua Medical Center	Honolulu	Hawaii
United States	Northwest Cancer Center	Houston	Texas
United States	Investigative Clinical Research Of Indiana, Llc	Indianapolis	Indiana
United States	Cancer Specialists of North FL	Jacksonville	Florida
United States	Cancer Center Of Acadiana	Lafayette	Louisiana
United States	Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Of Kentucky Markey Cancer Center	Lexington	Kentucky
United States	Local Institution	Long Beach	California
United States	Ucla Department Of Medicine	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical Oncology Care Associates	Orange	California
United States	Oncology Specialists, S.C.	Park Ridge	Illinois
United States	Pikeville Medical Center Leonard Lawson Cancer Center	Pikeville	Kentucky
United States	The Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Sharp Clinical Oncology Research	San Diego	California
United States	Local Institution	Seattle	Washington
United States	Local Institution	Shreveport	Louisiana
United States	Mercy Medical Research Institute	Springfield	Missouri
United States	Local Institution	Urbana	Illinois
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	Local Institution	Vallejo	California
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	Local Institution	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	AbbVie

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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 Fc?RIIIa V Allele	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 Fc?RIIIa V allele were a sub-set of all randomized participants.	Randomization until 111 events, up to May 2014, approximately 2 years
Secondary	Investigator-Assessed Objective Response Rate (ORR) - All Randomized Participants	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.	Randomization until 111 events, up to May 2014, approximately 2 years
Secondary	Investigator-Assessed Objective Response Rate in Randomized Participants With at Least One Fc?RIIIa V Allele	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 Fc?RIIIa V allele were a sub-set of all randomized participants.	Randomization until 111 events, up to May 2014, approximately 2 years

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