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Safety Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone for Multiple Myeloma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00560352
First received: November 16, 2007
Last updated: July 23, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to determine the safety and tolerability of dasatinib with bortezomib in the treatment of relapsed or refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: Dasatinib
Drug: Bortezomib
Drug: Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone 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:
  • Maximum Tolerated Dose (MTD) and Recommended MTD of Dasatinib in Combination With Bortezomib and Dexamethasone [ Time Frame: Days 1 to 21 ] [ Designated as safety issue: Yes ]
    MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended MTD is the maximum dose that the participants received.

  • MTD and Recommended MTD of Bortezomib in Combination With Dasatinib and Dexamethasone [ Time Frame: Days 1 to 21 ] [ Designated as safety issue: Yes ]
    MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended dose is the maximum dose that the participants received.


Secondary Outcome Measures:
  • Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry [ Time Frame: Day 1 until last tumor assessment (maximum reached: 9 months) ] [ Designated as safety issue: No ]
    S=serum; U=urine; MP=M-protein; ST=soft tissue, PC=plasmacytomas; IF=immunofixation; BL=baseline. RR calculated on best response any time. CR=MP undetectable by IF, ≤5% plasma cells in bone marrow, and no ST PC. VGPR=MP detectable by IF, or ≥90% drop in S MP and U MP<100 mg/24h. PR= ≥50% drop in S MP and ≥90% drop in U MP or U protein <200 mg/24h, ≥50% drop in BL ST PC size. MR= ≥25% to <50% drop in S MP and ≥50% to <90% drop in U MP and ≥25% to <50% drop in BL ST PC. SD=Not CR, VGPR, PR, or MR. PD= ≥25% rise in S or U M-component; new/increased size of bone lesions, ST PC, or hypercalcemia.

  • Duration of Response [ Time Frame: First occurrence of response to disease progression or death, whichever occurred first (maximum reached: 12.2 months) ] [ Designated as safety issue: No ]
    Duration of response calculated for those with best response=CR (M-protein [MP] undetectable by immunofixation [IF], ≤5% plasma cells in bone marrow, no soft tissue plasmacytomas); VGPR (MP detectable by IF, or ≥90% drop in serum [S] MP and urine [U] MP<100 mg/24h); PR(≥50% drop in S MP and ≥90% drop in U MP or U protein <200 mg/24h, ≥50% drop in BL ST PC size); or MR (≥25% to <50% drop in S MP and ≥50% to <90% drop in U MP and ≥25% to <50% drop in BL ST PC). Duration of response calculated from day criteria for CR, VGPR, PR, and MR were met until progression or death, whichever came first.

  • Progression-free Survival [ Time Frame: Day 1 to disease progression or death, whichever came first (maximum reached: 14 months) ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time from start of treatment until progression or death, whichever occurred first. Participants were to be followed-up for 12 months following the last dose of dasatinib for progression and survival. PFS was analyzed for the all-treated population.

  • Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade [ Time Frame: Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months) ] [ Designated as safety issue: Yes ]
    An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to or of unknown relationship to study treatment. Grade 3=severe; Grade 4=life-threatening.


Enrollment: 16
Study Start Date: February 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib + Bortezomib + Dexamethasone
Phase I dose escalation study
Drug: Dasatinib
Tablets; oral; approximately 2 years on study, depending on response; 50 mg once daily (QD), 100 mg QD, 140 mg QD
Other Names:
  • Sprycel
  • BMS-354825
Drug: Bortezomib
Powder; intravenous; approximately 2 years on study, depending on response; 1.0 mg/m^2 QD, 1.3 mg/m^2 QD
Other Name: Velcade®
Drug: Dexamethasone
Tablets; oral; approximately 2 years on study, depending on response; 20 mg QD

  Eligibility

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

Key Inclusion Criteria:

  • Confirmed diagnosis of multiple myeloma with measurable disease
  • Evidence of relapsed or refractory disease and at least 2 prior therapies for multiple myeloma
  • Eastern Cooperative Oncology Group Performance Status of 0 - 2
  • Last treatment for multiple myeloma not within 21 days prior to study treatment initiation
  • Bone marrow transplant not within 3 months prior to study treatment initiation
  • Required baseline hematology and chemistry parameters.

Key Exclusion Criteria:

  • Clinically significant cardiac disease (New York Heart Association Class III or IV)
  • Abnormal QT interval corrected for heart rate using Fridericia's formula prolonged (>450 msec) after electrolytes have been corrected on baseline electrocardiogram
  • Malabsorption syndrome or uncontrolled gastrointestinal toxicities
  • Dementia, chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation
  • Clinically significant pleural effusion in the previous 12 months or current ascites
  • Clinically significant coagulation or platelet function disorder
  • Intolerance to dasatinib and/or bortezomib
  • Acute diffuse infiltrative pulmonary disease
  • Prior or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer currently in complete remission, cervical carcinoma in situ, or any other cancer from which the participant has been disease-free for 3 years.
  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: NCT00560352

Locations
United States, Florida
Orlando Health, Inc. M.D. Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
France
Local Institution
Nantes, Cedex 1, France, 44093
Local Institution
Lille Cedex, France, 59037
Italy
Local Institution
Bari, Italy, 70124
Local Institution
Bologna, Italy, 40138
Spain
Local Institution
Salamanca, Spain, 37007
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00560352     History of Changes
Other Study ID Numbers: CA180-181
Study First Received: November 16, 2007
Results First Received: April 2, 2012
Last Updated: July 23, 2012
Health Authority: United States: Food and Drug Administration
Spain: Ministry of Health and Consumption
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
France: Ministry of Health

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dasatinib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on November 25, 2014