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

Multiple Myeloma Clinical Trial

Official title:

A Phase I Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00560352
• Other study ID #: CA180-181
• Status: Terminated
• Phase: Phase 1
• First received: November 16, 2007
• Last updated: July 23, 2012
• Start date: February 2008
• Est. completion date: February 2011

Study information

• Verified date: July 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSpain: Ministry of Health and ConsumptionItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthFrance: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Dasatinib
Tablets; oral; approximately 2 years on study, depending on response; 50 mg once daily (QD), 100 mg QD, 140 mg QD
• Bortezomib
Powder; intravenous; approximately 2 years on study, depending on response; 1.0 mg/m^2 QD, 1.3 mg/m^2 QD
• Dexamethasone
Tablets; oral; approximately 2 years on study, depending on response; 20 mg QD

Locations

Country	Name	City	State
France	Local Institution	Lille Cedex
France	Local Institution	Nantes	Cedex 1
Italy	Local Institution	Bari
Italy	Local Institution	Bologna
Spain	Local Institution	Salamanca
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Orlando Health, Inc. M.D. Anderson Cancer Center Orlando	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) and Recommended MTD of Dasatinib in Combination With Bortezomib and Dexamethasone	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.	Days 1 to 21	Yes
Primary	MTD and Recommended MTD of Bortezomib in Combination With Dasatinib and Dexamethasone	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.	Days 1 to 21	Yes
Secondary	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	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.	Day 1 until last tumor assessment (maximum reached: 9 months)	No
Secondary	Duration of Response	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.	First occurrence of response to disease progression or death, whichever occurred first (maximum reached: 12.2 months)	No
Secondary	Progression-free Survival	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.	Day 1 to disease progression or death, whichever came first (maximum reached: 14 months)	No
Secondary	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	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.	Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form