Back to resultsA 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
Primary Purpose
Leukemia
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Dasatinib
Imatinib
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring Leukemia (chronic myeloid leukemia - chronic phase)
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Sites / Locations
- Dr. Marshall Schreeder
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- M.D. Anderson Cancer Center Orlando
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- New York Presbyterian Hospital
- New York Medical College
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Local Institution
- Santee Hematology/Oncology
- Local Institution
- Local Institution
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
A
B
Arm Description
50-180 mg once daily (QD)
200-800 mg QD
Outcomes
Primary Outcome Measures
Complete Cytogenetic Response (CCyR) Rate at 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
Major Molecular Response (MMR) Rates
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
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
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)
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00362466
Brief Title
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
Official Title
An Open-Label Randomized Phase III Study of Dasatinib vs. High-Dose (600 mg) Imatinib Mesylate in the Treatment of Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Are Imatinib Failures or Who Have Had a Suboptimal Response After 3-18 Months of Therapy With 400 mg Imatinib
Study Type
Interventional
2. Study Status
Record Verification Date
November 2009
Overall Recruitment Status
Terminated
Why Stopped
Insufficient Enrollment
Study Start Date
April 2007 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
Leukemia (chronic myeloid leukemia - chronic phase)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Active Comparator
Arm Description
50-180 mg once daily (QD)
Arm Title
B
Arm Type
Active Comparator
Arm Description
200-800 mg QD
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Other Intervention Name(s)
Sprycel®
Intervention Description
Tablets, Oral, Once daily, 5-7 years
Intervention Type
Drug
Intervention Name(s)
Imatinib
Intervention Description
Tablets, Oral, Once daily, 5-7 years
Primary Outcome Measure Information:
Title
Complete Cytogenetic Response (CCyR) Rate at Month 6
Description
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.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Major Molecular Response (MMR) Rates
Description
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.
Time Frame
Month 3, Month 6, Month 12, Month 24 and Month 36
Title
CCyR Rates
Description
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.
Time Frame
Month 3, Month 12, Month 24 and Month 36
Title
Estimate Time to MMR and CCyR
Description
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.
Time Frame
throughout the study
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
at 36 months
Title
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs
Description
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.
Time Frame
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.
Title
Duration of CCyR and MMR
Description
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.
Time Frame
Throughout the study
Title
Best MMR Rates
Description
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.
Time Frame
throughout study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Dr. Marshall Schreeder
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
Local Institution
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Local Institution
City
Alhambra
State/Province
California
ZIP/Postal Code
91801
Country
United States
Facility Name
Local Institution
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Local Institution
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Local Institution
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
Local Institution
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Local Institution
City
La Verne
State/Province
California
ZIP/Postal Code
91750
Country
United States
Facility Name
Local Institution
City
Long Beach
State/Province
California
ZIP/Postal Code
90813
Country
United States
Facility Name
Local Institution
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Local Institution
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Local Institution
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Local Institution
City
Northridge
State/Province
California
ZIP/Postal Code
91325
Country
United States
Facility Name
Local Institution
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Local Institution
City
Redondo Beach
State/Province
California
ZIP/Postal Code
90277
Country
United States
Facility Name
Local Institution
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Local Institution
City
Santa Maria
State/Province
California
ZIP/Postal Code
93454
Country
United States
Facility Name
Local Institution
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Local Institution
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Local Institution
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Local Institution
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
M.D. Anderson Cancer Center Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Local Institution
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Local Institution
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Local Institution
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Local Institution
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Local Institution
City
Hazard
State/Province
Kentucky
ZIP/Postal Code
41701
Country
United States
Facility Name
Local Institution
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Local Institution
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Local Institution
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Local Institution
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Local Institution
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
Local Institution
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Local Institution
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Local Institution
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Local Institution
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Local Institution
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Local Institution
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74136
Country
United States
Facility Name
Local Institution
City
Baltimore
State/Province
Pennsylvania
ZIP/Postal Code
21229
Country
United States
Facility Name
Local Institution
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Santee Hematology/Oncology
City
Sumter
State/Province
South Carolina
ZIP/Postal Code
29150
Country
United States
Facility Name
Local Institution
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Local Institution
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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