Study of Mapatumumab in Combination With Bortezomib (Velcade) and Bortezomib Alone in Subjects With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy (disease response) and safety of mapatumumab in combination with bortezomib and bortezomib alone in subjects with relapsed or refractory multiple myeloma (MM).

Official Title
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A Phase 2, Multi-Center, Open-Label, Randomized Study of Mapatumumab (TRM-1 [HGS1012], a Fully Human Monoclonal Antibody to TRAIL-R1) in Combination With Bortezomib (Velcade) and Bortezomib Alone in Subjects With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Mapatumumab
* Biological: Mapatumumab
* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with multiple myeloma that is refractory or has relapsed after treatment Measurable serum and/or urine M-protein Failed 1 or 2 prior therapies for multiple myeloma 18 years of age or older Exclusion Criteria: Received more than 2 prior therapies for multiple myeloma. Previous cancer therapies (chemotherapy, biologic therapy, radiation therapy or immunosuppressants) within the last 3 weeks Received monoclonal antibodies within the last 3 weeks (chimeric or murine) or 8 weeks (human or humanized) Received investigational (not yet approved by a regulatory authority) agent to treat multiple myeloma within the last 4 weeks Subjects who received a stem cell transplant using cells from themselves in the past 16 weeks Subjects who received a stem cell transplant using cells from another individual Previously treated with bortezomib or mapatumumab Known HIV, hepatitis-B, hepatitis-C, or hepatitis A infection Infection requiring antibiotics or hospitalization within the last 2 weeks Major surgery within the last 4 weeks Diagnosis with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) History of other cancers within the past 5 years Pregnant or breast-feeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Bortezomib | Drug: Bortezomib<br>* 1.3 mg/m^2 IV (in the vein), twice weekly for two weeks (Days 1, 4, 8, and 11) of each 21-day cycle. Number of cycles: Treatment will continue for up to 17 cycles, or until disease progression or unacceptable toxicity.<br>* Other names: Velcade;|
| Experimental: B-10<br>Bortezomib and Mapatumumab 10 mg/kg | Biological: Mapatumumab<br>* 10 mg/kg IV (in the vein), on day 1 of each 21-day cycle. Number of cycles: Treatment will continue for up to 17 cycles, or until disease progression or unacceptable toxicity.<br>Drug: Bortezomib<br>* 1.3 mg/m^2 IV (in the vein), twice weekly for two weeks (Days 1, 4, 8, and 11) of each 21-day cycle. Number of cycles: Treatment will continue for up to 17 cycles, or until disease progression or unacceptable toxicity.<br>* Other names: Velcade;|
| Experimental: B-20<br>Bortezomib and Mapatumumab 20 mg/kg | Biological: Mapatumumab<br>* 20 mg/kg IV (in the vein), on day 1 of each 21-day cycle. Number of cycles: Treatment will continue for up to 17 cycles, or until disease progression or unacceptable toxicity.<br>Drug: Bortezomib<br>* 1.3 mg/m^2 IV (in the vein), twice weekly for two weeks (Days 1, 4, 8, and 11) of each 21-day cycle. Number of cycles: Treatment will continue for up to 17 cycles, or until disease progression or unacceptable toxicity.<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate disease response to mapatumumab in combination with bortezomib and bortezomib alone |  | 17 cycles (up to a year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety, including the frequency and severity of adverse events and laboratory abnormalities, of mapatumumab in combination with bortezomib and bortezomib alone throughout the study period |  | 17 cycles (up to a year) |