Safety Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone for Multiple Myeloma
This study has been terminated.
Sponsor:
Bristol-Myers Squibb
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
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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:
Drug Information available for:
Dexamethasone
Dexamethasone acetate
Dexamethasone sodium phosphate
Bortezomib
Dasatinib
U.S. FDA Resources
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:
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
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 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 Bortezomib BB 1101 Dasatinib 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 June 18, 2013