A Phase II Study of BMS-354825 in Subjects With Myeloid Blast Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate

Bristol-Myers Squibb1 site in 1 country124 target enrollmentDecember 2004

ConditionsChronic Myeloid Leukemia Blast Crisis

InterventionsDasatinib

DrugsDasatinib

Overview

Phase: Phase 2
Intervention: Dasatinib
Conditions: Chronic Myeloid Leukemia
Sponsor: Bristol-Myers Squibb
Enrollment: 124
Locations: 1
Primary Endpoint: Major and Overall Hematologic Response (MaHR and OHR)
Status: Completed
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to see what effect an investigational drug (BMS-354825) has on subjects who are currently in the myeloid blast phase of chronic myeloid leukemia (CML) and who are either resistant to or intolerant of imatinib mesylate. Another purpose of the study is to see what side effects this drug may have on subjects.

Registry

clinicaltrials.gov

Start Date

December 2004

End Date

March 2008

Last Updated

15 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Eligibility Criteria

Inclusion Criteria

•Subjects with myeloid blast phase chronic myeloid leukemia
•Subjects who are either resistant or intolerant of imatinib mesylate

Exclusion Criteria

•Subjects who are eligible and willing to undergo transplantation
•Serious uncontrolled medical disorder or active infection
•Uncontrolled or significant heart problems, such as congestive heart failure, recent heart attack, etc
•Subjects receiving medications that may affect heart rhythm
•Other malignancy/cancer other than CML
•History of significant bleeding disorder unrelated to CML
•Pregnant or breastfeeding women (subjects must avoid becoming pregnant)
•Subjects received imatinib within 7 days, interferon or cytarabine within 14 days, a targeted anticancer medication within 14 days, an antineoplastic agent (other than hydroxyurea or anagrelide) within 28 days, or any other investigation medication in 28 days
•Subject is receiving medications that affect platelet function or an anticoagulant

Arms & Interventions

1

Intervention: Dasatinib

Outcomes

Primary Outcomes

Major and Overall Hematologic Response (MaHR and OHR)

Time Frame: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment

MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts + promyelocytes in bone marrow and \<30% blasts + promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.

Secondary Outcomes

Median Duration of Major Hematologic Response (MaHR)(Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment)
Median Duration of Overall Hematologic Response (OHR)(Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment)
Time to MaHR and OHR(Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment)
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response(Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment)
Number of Participants With CHR or NEL, MiHR, or no Hematologic Response(Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycles 1 and 2; After every 2nd cycle for Cycles 3+; at end of treatment)
Number of Participants Achieving Major Molecular Response (MMR)(Baseline, every 12 weeks, and at time of Complete Cytogenetic Response (CCyR) for quantitative Polyermase Chain Reaction (qPCR) analysis)
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations(baseline, at time of disease progression)
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)(Baseline, Every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up)
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs(Continuously throughout study, from pre-treatment visit through end of study (due to death, unacceptable toxicity, treatment failure, etc) and follow-up period)
Pharmacokinetics (PK) of Dasatinib - Maximum Observed Plasma Concentration (Cmax)(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h or 24 h(AUC[0-T])(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib - Time to Maximum Observed Plasma Concentration (Tmax)(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib - Plasma Half-life (T-HALF)(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h (AUC[0-T])(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)(Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.)
Population PK of Dasatinib(Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.)