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

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

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).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib; Biological: Mapatumumab; Biological: Mapatumumab

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Department of Haematology, Royal North Shore Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Institute of Medical & Veterinary Science
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Peter MacCallum Cancer Centre
    • Melbourne, Victoria, Australia, 3181
      • Clinical Haematology & BMT, Alfred Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Health Research Institute - General Campus
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Notre Dame Centre Hospitalier de l'Universite de Montreal
• India
  • Bangalore, India, 560027
    • Bangalore Institute of Oncology
  • New Delhi, India, 110 029
    • All India Institute of Medical Sciences
  • New Delhi, India, 110 085
    • Rajiv Gandhi Cancer Institute & Research Center
  • Karnataka
    • Mysore, Karnataka, India, 570 017
      • Bharath Hospital & Institute of Oncology
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic Medical Group, Inc.
  • Florida
    • Lecanto, Florida, United States, 34461
      • Cancer and Blood Disorders Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Missouri
    • Jefferson City, Missouri, United States, 65109
      • Capitol Comprehensive Cancer Care Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Bortezomib	Drug: Bortezomib; 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.; Other Names: Velcade
Experimental: B-10; Bortezomib and Mapatumumab 10 mg/kg	Drug: Bortezomib; 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.; Other Names: Velcade; Biological: Mapatumumab; 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.; Biological: Mapatumumab; 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.
Experimental: B-20; Bortezomib and Mapatumumab 20 mg/kg	Drug: Bortezomib; 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.; Other Names: Velcade; Biological: Mapatumumab; 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.; Biological: Mapatumumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc.
• Investigators: Study Chair: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: April 17, 2006
• First Submitted That Met QC Criteria: April 17, 2006
• First Posted (Estimate): April 19, 2006

Study Record Updates

• Last Update Posted (Estimate): August 8, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Bortezomib; Antibodies, Monoclonal; Mapatumumab
• Other Study ID Numbers: HGS1012-C1055