Leukemia
Conditions
Keywords
Leukemia (chronic myeloid leukemia - chronic phase)
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.
Interventions
DRUGDasatinib
Tablets, Oral, Once daily, 5-7 years
DRUGImatinib
Tablets, Oral, Once daily, 5-7 years
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 156 subjects were to be enrolled; however, the attempts were unsuccessful and the study was closed after 3 subjects were enrolled. A fourth subject underwent screening, but was not randomized since the subject did not meet the inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib 100 mg QD | 2 |
| Imatinib 600 mg QD | 1 |
| Total | 3 |
Baseline characteristics
| Characteristic | Dasatinib | Imatinib | Total |
|---|---|---|---|
| Age Continuous 30- to 39-years-old | 1 Participants | 0 Participants | 1 Participants |
| Age Continuous 40- to 49-years-old | 1 Participants | 0 Participants | 1 Participants |
| Age Continuous 50- to 59-years-old | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
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.
Time frame: Month 6
Population: This analysis was not done. This study was terminated due to insufficient enrollment.
Secondary
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.
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.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | AEs | 3 events |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | SAEs | 0 events |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | AEs leading to Discontinuation | 0 events |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | Deaths | 0 events |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | Deaths | 0 events |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | AEs | 1 events |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | AEs leading to Discontinuation | 0 events |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs | SAEs | 0 events |
Secondary
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.
Time frame: throughout study
Population: This analysis was not done. This study was terminated due to insufficient enrollment.
Secondary
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.
Time frame: Month 3, Month 12, Month 24 and Month 36
Population: This analysis was not done. This study was terminated due to insufficient enrollment.
Secondary
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.
Time frame: Throughout the study
Population: This analysis was not done. This study was terminated due to insufficient enrollment.
Secondary
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.
Time frame: throughout the study
Population: This analysis was not done. This study was terminated due to insufficient enrollment.
Secondary
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.
Time frame: Month 3, Month 6, Month 12, Month 24 and Month 36
Population: This analysis was not done. This study was terminated due to insufficient enrollment.
Secondary
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.
Time frame: at 36 months
Population: This analysis was not done. This study was terminated due to insufficient enrollment.