Multiple Ascending Dose (MAD) Combination in Subjects With Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00884546
First received: April 16, 2009
Last updated: July 12, 2012
Last verified: July 2012
  Purpose

To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of BMS-833923 administered alone, in combination with lenalidomide plus dexamethasone, or in combination with bortezomib in subjects with relapsed or refractory multiple myeloma.


Condition Intervention Phase
Advanced Cancer, Various, NOS
Drug: BMS-833923
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Bortezomib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Multiple Ascending Dose Study of BMS-833923 Alone or in Combination With Lenalidomide (Revlimid) Plus Dexamethasone or in Combination With Bortezomib (Velcade) in Subjects With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • To establish DLT(s), MTD, and Phase 2 dose range and schedule of BMS-833923 administered alone, in combination with two dose levels of lenalidomide plus dexamethasone, or with two dose levels of bortezomib in subjects with relapsed or refractory MM [ Time Frame: For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of BMS-833923 as a single agent or in combination with two dose levels of lenalidomide plus a fixed low-dose of dexamethasone or in combination with two dose levels of bortezomib [ Time Frame: For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles ] [ Designated as safety issue: Yes ]
  • To evaluate the Pharmacokinetics of BMS-833923 [ Time Frame: For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles ] [ Designated as safety issue: No ]
  • To evaluate the Pharmacodynamics effects of BMS-833923 [ Time Frame: For Treatment Arms A and B, outcome would be measured for approximately 5 months on Days 1, 8, 15, and 28 for Cycles 1 and 2 and then every 28 days for the following cycles ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: July 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
BMS-833923 (Starting dose is a loading dose of 60 mg for 7 days with a 30 mg daily dose thereafter)
Drug: BMS-833923
Capsule, Oral, Once daily, 6 months
Active Comparator: Arm 2

BMS-833923 (MTD or below)

Lenalidomide (at or below the recommended prescribing dose)

Dexamethasone (40 mg)

Drug: BMS-833923
Capsule, Oral, Once daily, 6 months
Drug: Lenalidomide
Capsule, Oral, Once daily, 6 months
Other Name: Revlimid
Drug: Dexamethasone
Capsule, Oral, Once a week, 6 months
Active Comparator: Arm 3

BMS-833923 (MTD or below)

Bortezomib (at or below the recommended prescribing dose)

Drug: BMS-833923
Capsule, Oral, Once daily, 6 months
Drug: Bortezomib
Powder, IV, On days 1, 4, 8, 11, 6 months
Other Name: Velcade

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of Multiple Myeloma
  • Men and Women at least 18 years old
  • ECOG status 0-2
  • Last therapeutic or diagnostic treatment at least 21 days prior
  • Bone marrow transplants must have been completed at least 3 months prior
  • Any toxicity from prior therapies must have resolved to Grade ≤1

Exclusion Criteria:

  • Women pregnant or breastfeeding
  • WOCBP unwilling/unable to use acceptable method to avoid pregnancy
  • Uncontrolled medical disorder or active infection
  • Current or recent (w/in 3 months) gastrointestinal disorder
  • Inability to swallow oral medication
  • Inability to be venipunctured
  • Uncontrolled or significant cardiovascular disease
  • Uncontrolled hyperlipidemia
  • Intolerance of lenalidomide or bortezomib if participating in Arms B and C
  • Concurrent therapy with any other investigational product
  • Subjects involuntary incarcerated
  • Subjects detained for treatment of psychiatric or physical illness
  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: NCT00884546

Locations
United States, California
City Of Hope National Medical Center
Duarte, California, United States, 91010
Moores Ucsd Cancer Center
La Jolla, California, United States, 92093
Local Institution
Los Angeles, California, United States, 90048
United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
United States, Michigan
Local Institution
Detroit, Michigan, United States, 48201
United States, New Jersey
John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601
United States, Texas
Oncology Consultants, Pa
Houston, Texas, United States, 77024
Cancer Therapy And Research Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Bristol-Myers Squibb
Exelixis
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00884546     History of Changes
Other Study ID Numbers: CA194-003
Study First Received: April 16, 2009
Last Updated: July 12, 2012
Health Authority: United States: Food and Drug Administration

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
Lenalidomide
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 16, 2014