A Study of Dasatinib vs. High-Dose Imatinib (600 mg) in Patients With Chronic Phase Chronic Myeloid Leukemia (CML) Who Failed to Achieve Complete Cytogenetic Response After 3-18 Months of Imatinib Therapy
- Registration Number
- NCT00362466
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this clinical research study is to compare the rate of complete cytogenetic response of dasatinib to imatinib therapy at 6 months after randomization in chronic phase CML patients. The safety of this treatment will also be studied.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
- Men and women ≥18 years diagnosed with Chronic Phase Philadelphia chromosome positive (CP Ph+) CML who have failed to achieve CCyR after 3-18 months of therapy with imatinib 400 mg
- Treatment initiation with imatinib 400 mg within 6 months of initial CML diagnosis
- Able to tolerate chronic administration of imatinib at the highest dose (400-600 mg) the subject has received in the past
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2
- Adequate hepatic and renal function
- Eligible and willing to undergo immediate autologous/allogeneic stem cell transplant
- Previous diagnosis of accelerated/blast crisis CML
- Subjects with clonal evolution in Ph+ cells observed in ≥2 metaphases
- Previous documentation of T315I mutation
- Uncontrolled or significant cardiovascular disease
- Serious uncontrolled medical disorder/active infection
- History of significant bleeding disorder unrelated to CML
- Intolerance to imatinib ≥400 mg
- Concurrent malignancies other than CML
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A Dasatinib 50-180 mg once daily (QD) B Imatinib 200-800 mg QD
- Primary Outcome Measures
Name Time Method Complete Cytogenetic Response (CCyR) Rate at Month 6 Month 6 Cytogenetic Response (CyR) is based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.
- Secondary Outcome Measures
Name Time Method Major Molecular Response (MMR) Rates Month 3, Month 6, Month 12, Month 24 and Month 36 MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as percent of ratio of BCR-ABL gene transcripts to the control gene. In this study,ABL was used as the control gene.
CCyR Rates Month 3, Month 12, Month 24 and Month 36 CyR is based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. The criteria for CCyR is 0% Ph+ metaphases among cells in a bone marrow sample.
Estimate Time to MMR and CCyR throughout the study Time to MMR is defined as the time from first treatment dose until measurement criteria are first met for MMR. Time to MMR is computed only for subjects who achieved a MMR. Time to CCyR is defined as the time from first treatment dose until measurement criteria are first met for CCyR. Time to CCyR is computed only for subjects who achieved a CCyR.
Progression Free Survival (PFS) at 36 months PFS=time from randomization until progression or death. Participants who died without progression=progression on date of death. Participants who neither progressed nor died were censored on date of last hematologic assessment. Participants who did not receive study treatment and neither progressed nor died were censored on date of randomization.
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs From 2 weeks prior to randomization through Month 36. At least every 4 weeks until all study-related toxicities resolve to baseline, stabilize, or are deemed irreversible. An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Duration of CCyR and MMR Throughout the study Duration of CCyR computed for subjects with CCyR as best response; measured from time the criteria are first met for CCyR until date of progression or death. Duration of MMR computed for subjects with MMR as best response; measured from time the criteria are first met for MMR until date the MMR was first lost, disease progression or death.
Best MMR Rates throughout study MMR is defined as a 3-log reduction in BCR-ABL gene transcripts from a standardized baseline. Reductions in BCR-ABL transcripts on logarithmic scale are calculated based on the absolute values expressed as % of ratio of BCR-ABL gene transcripts to the control gene. In this study, ABL was used as the control gene.
Trial Locations
- Locations (6)
Santee Hematology/Oncology
🇺🇸Sumter, South Carolina, United States
M.D. Anderson Cancer Center Orlando
🇺🇸Orlando, Florida, United States
Local Institution
🇺🇸Houston, Texas, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Dr. Marshall Schreeder
🇺🇸Huntsville, Alabama, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States