A Phase II Study to Determine the Activity of BMS-354825 in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to High Dose Imatinib Mesylate (Gleevec) or Who Are Intolerant of Imatinib

Bristol-Myers Squibb2 sites in 2 countries387 target enrollmentFebruary 2005

ConditionsChronic Myeloid Leukemia Philadelphia-Positive Myeloid Leukemia

InterventionsDasatinib

DrugsDasatinib

Overview

Phase: Phase 2
Intervention: Dasatinib
Conditions: Chronic Myeloid Leukemia
Sponsor: Bristol-Myers Squibb
Enrollment: 387
Locations: 2
Primary Endpoint: Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)
Status: Completed
Last Updated: 14 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.

Registry

clinicaltrials.gov

Start Date

February 2005

End Date

April 2008

Last Updated

14 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age of 18 years and older.
•Chronic myeloid leukemia (CML)
•Previous treatment with imatinib at a dose of \>600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR
•CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR
•Intolerance to imatinib at any dose
•Adequate organ function
•Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.

Exclusion Criteria

•Woman who are pregnant or breastfeeding
•Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above
•Previous diagnosis of accelerated phase or blast crisis CML.
•Participants who are eligible and willing to undergo transplantation during the screening period
•Uncontrolled or significant cardiovascular disease
•Use of imatinib within 7 days.
•Use of interferon or cytarabine within 14 days
•Use of a targeted small-molecule anticancer agent within 14 days
•Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants
•Prior therapy with dasatinib.

Arms & Interventions

Dasatinib, 70 mg twice daily (BID)

Dasatanib, 70 mg twice daily (BID), with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance.

Intervention: Dasatinib

Outcomes

Primary Outcomes

Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)

Time Frame: 2 years

Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.

Secondary Outcomes

Number of Imatinib-intolerant Participants With MCyR(Baseline to 2 years)
Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months(12 and 24 Months)
Median Time From First Dosing Date to Date of MCyR(Baseline (within 4 weeks of Day 1) and every 12 weeks)
Number of Participants With Complete Hematologic Response (CHR)(Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study)
Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months(12 and 24 months)
Median Time From First Dosing Until CHR(Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study)
Number of Participants With Major Molecular Response (MMR)(Baseline to 2 years)
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores(Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.)
Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE(Continuously, from baseline through 2 years)
Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE(Continuously, from baseline through 2 years)
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib(Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.)