Clinical trial NCT00482703: A Study of Dasatinib in Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia
Official title: A Randomized, Multicenter, Open-label Phase II Study of Dasatinib (BMS-354825) Administered Orally at a Dose of 50mg Twice Daily or 100mg Once Daily in Subjects With Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia Who Are Resistant or Intolerant to Imatinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Myeloid Leukemia, Chronic
Keywords: Imatinib resistant or intolerant chronic phase CML
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-06-05
Enrollment: 23
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective is to evaluate the cytogenetic response to Dasatinib (BMS-354825) administered for 24 weeks in subjects with Imatinib resistant or intolerant chronic phase chronic myeloid leukemia (CML) once daily (QD) or twice daily. (BID)


Eligibility criteria: Inclusion Criteria:

* Philadelphia chromosome positive or bcr-abl gene positive Chronic phase Chronic Myelogenous Leukemia (CML) subjects must have primary or acquired resistance to Imatinib mesylate or have intolerance of imatinib mesylate
* Performance status (general conditions) specified by the Eastern Cooperative Oncology Group: 0-2
* Men and women, ages 20 to 75
* Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized

Exclusion Criteria:

* Subjects who are eligible and willing to undergo transplantation at pre-study
* Women who are pregnant or breastfeeding
* Uncontrolled or significant cardiovascular disease
* History of significant bleeding disorder unrelated to CML
* Adequate hepatic function
* Adequate renal function
* Medication that increases bleeding risk
* Medication that changes heart rhythms
* Subjects who are compulsory detained for legal reasons or treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study

Primary outcomes:
measure: Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
timeFrame: Throughout study period to last observation. Dosing period=6 months; if beneficial, medication may continue in the extension period (ending in January 2009). Last observation=30 days past last dosing day or the discontinuation day.
measure: Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
timeFrame: Week 24
measure: Time to Major Cytogenetic Response (MCyR)
timeFrame: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met
measure: Pharmacokinetics of Dasatinib (BMS-354825) as Characterized by Population Pharmacokinetics
timeFrame: Six or more peripheral blood samples were collected at any visit after Day 7, pre-dose and 5 - 8 hours after dose administration.
measure: Duration of MCyR
timeFrame: from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death
measure: Time to CHR
timeFrame: time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are met
measure: Duration of CHR
timeFrame: measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death
measure: Progression-Free Survival (PFS)
timeFrame: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met
measure: Expression of BCR-ABL Gene Mutations of RNA (mRNA)
timeFrame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
measure: Mutational Spectrum of BCR-ABL
timeFrame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
measure: Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
timeFrame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
measure: Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
timeFrame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Other outcomes:
measure: Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
timeFrame: Months 0, 4, 8, 12, 16, 20, 24
measure: Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
timeFrame: Months 0, 4, 8, 12, 16, 20, 24
measure: Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
timeFrame: Months 0, 4, 8, 12, 16, 20, 24
Locations:
city: Nagoya
country: Japan
facility: Local Institution
state: Aichi
city: Nishinomiya-Shi
country: Japan
facility: Local Institution
state: Hyogo
city: Kagoshima-Shi
country: Japan
facility: Local Institution
state: Kagoshima
city: Isehara-Shi
country: Japan
facility: Local Institution
state: Kanagawa
city: Hamamatsu-Shi
country: Japan
facility: Local Institution
state: Shizuoka
city: Bunkyo-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Chuo-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Shibuya-Ku
country: Japan
facility: Local Institution
state: Tokyo
city: Kyoto
country: Japan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: