Leukemia
Conditions
Keywords
Myelogenous, Chronic, BCR-ABL Positive
Brief summary
The purpose of the study is to compare response rates in newly diagnosed Chronic Phase (CP) CML subjects treated with dasatinib plus BMS-833923 versus dasatinib alone.
Detailed description
1. Design: Study Design and Duration as current described are no longer applicable since enrollment was prematurely concluded due to a decision by the sponsor. Subjects currently enrolled in the trial will continue to receive dasatinib alone at a starting dose of 100 mg QD for: 1. a maximum of 5 years after entry into the study 2. until progression by Investigators determination/judgment 3. intolerance to Dasatinib 4. the study is terminated due to safety concerns or 5. other administrative reasons as communicated by the sponsor 2. Research Hypothesis : The research hypothesis and primary objective of this study as originally designed are no longer applicable as subjects enrolment has been terminated due to administrative reasons by the sponsor. The objective of the altered design of this study is to describe the safety profile and tolerability of dasatinib
Interventions
DRUGDasatinib
Tablets, Oral, 100 mg, Once daily, approximately 5 years depending on response
DRUGBMS-833923
Capsules, Oral, dose to be determined, Once daily, approximately 2 years depending on response
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
* Subjects ≥ 18 years of age who have signed informed consent * Philadelphia positive Chronic Myeloid Leukemia (CML) in chronic phase * Previously untreated chronic phase CML, except for Anagrelide or Hydroxyurea. * Eastern Co-Operative Group (ECOG) Performance Status (PS) Score 0 - 2
Exclusion criteria
* Known Abl-kinase T315I or T315A mutation * Serious or uncontrolled medical disorder (including infection or cardiovascular disease) or dementia or other serious psychiatric condition * Prior chemotherapy. * Women who are pregnant or breastfeeding or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy during the entire study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Molecular Response | Baseline up to 12 months | Major molecular response (MMR) was assessed using BCR-ABL transcript levels measured by real-time quantitative polymerase chain reaction (qPCR). MMR was defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value). Number of participants with MMR by timepoint are cumulative. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Molecular Response at Any Time | Baseline to End of study (approximately 48 months) | — |
| Progression-free Survival, Measured by the Time From Start of Treatment to Progression or Death | Baseline to End of study (approximately 48 months) | — |
| Event-free Survival, Measured by the Time From Start of Treatment to Progression, Death or Treatment Discontinuation | Baseline to End of study (approximately 48 months) | — |
| Transformation-free Survival Measured by the Time From Start of Treatment to Criteria for Accelerated or Blast Phase CML Are Met and Death | Baseline to End of study (approximately 48 months) | — |
| Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death | From date of first dose of study treatment up to the date of the last dose plus 30 days (approximately 49 months) | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug. |
Countries
Argentina, Belgium, Canada, Finland, France, Poland, Spain, United States
Participant flow
Pre-assignment details
70 participants were enrolled, 66 were treated. Reasons for non-treatment include 1 adverse event and 3 no longer met study criteria. Participants enrolled were only treated with Dasatinib. The Dasatinib + SMO antagonist (BMS-833923) arm did not have participants because the recommended phase 2 dose of the SMO antagonist had not been determined.
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib Dasatinib: Tablets, Oral, 100 mg, were given once daily for approximately 1 year before the study was terminated. | 66 |
| Dasatinib + SMO Antagonist (BMS-833923) No participants were randomized to this arm because no recommended phase 2 dose of the SMO antagonist could be determined (in a separate trial).
Dasatinib for 1 year followed by dasatinib plus SMO antagonist (BMS-833923) for 2 years followed by dasatinib alone for approximately 2 years; depending on response Dasatinib: Tablets, Oral, 100 mg, Once daily BMS-833923: Capsules, Oral, dose to be determined, Once daily, approximately 2 years depending on response | 0 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Reason by Sponsor | 45 | 0 |
| Overall Study | Adverse Event Unrelated to Study Drug | 3 | 0 |
| Overall Study | Disease Progression | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Maximum Clinical Benefit | 2 | 0 |
| Overall Study | Reason Unspecified | 1 | 0 |
| Overall Study | Study Drug Toxicity | 11 | 0 |
| Overall Study | Subject Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Dasatinib | Dasatinib + SMO Antagonist (BMS-833923) | Total |
|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 12 Participants | 0 Participants | 12 Participants |
| Age, Customized Between 18 and 64 years | 54 Participants | 0 Participants | 54 Participants |
| Sex: Female, Male Female | 27 Participants | 0 Participants | 27 Participants |
| Sex: Female, Male Male | 39 Participants | 0 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 66 |
| other Total, other adverse events | 60 / 66 |
| serious Total, serious adverse events | 18 / 66 |
Outcome results
Primary
Number of Participants With Major Molecular Response
Major molecular response (MMR) was assessed using BCR-ABL transcript levels measured by real-time quantitative polymerase chain reaction (qPCR). MMR was defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value). Number of participants with MMR by timepoint are cumulative.
Time frame: Baseline up to 12 months
Population: Efficacy Sample: all treated participants with at least one assessment on treatment. Participants enrolled in this trial could not be randomized to the Dasatinib + SMO antagonist arm because no recommended phase 2 dose of the SMO antagonist could be determined (in a separate trial).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dasatinib | Number of Participants With Major Molecular Response | Baseline | 1 Participants |
| Dasatinib | Number of Participants With Major Molecular Response | 6 Months | 30 Participants |
| Dasatinib | Number of Participants With Major Molecular Response | 3 Months | 9 Participants |
| Dasatinib | Number of Participants With Major Molecular Response | 12 Months | 34 Participants |
| Dasatinib + SMO Antagonist (BMS-833923) | Number of Participants With Major Molecular Response | 3 Months | 0 Participants |
| Dasatinib + SMO Antagonist (BMS-833923) | Number of Participants With Major Molecular Response | Baseline | 0 Participants |
| Dasatinib + SMO Antagonist (BMS-833923) | Number of Participants With Major Molecular Response | 12 Months | 0 Participants |
| Dasatinib + SMO Antagonist (BMS-833923) | Number of Participants With Major Molecular Response | 6 Months | 0 Participants |
Secondary
Complete Molecular Response at Any Time
Time frame: Baseline to End of study (approximately 48 months)
Population: The study was terminated prior to data collection for this endpoint.
Secondary
Event-free Survival, Measured by the Time From Start of Treatment to Progression, Death or Treatment Discontinuation
Time frame: Baseline to End of study (approximately 48 months)
Population: The study was terminated prior to data collection for this endpoint.
Secondary
Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug.
Time frame: From date of first dose of study treatment up to the date of the last dose plus 30 days (approximately 49 months)
Population: All Treated Participants; Participants enrolled in this trial could not be randomized to the Dasatinib + SMO antagonist arm because no recommended phase 2 dose of the SMO antagonist could be determined (in a separate trial).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death | SAE | 18 participants |
| Dasatinib | Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death | Drug-Related AE | 56 participants |
| Dasatinib | Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death | Death | 2 participants |
| Dasatinib | Number of Participants Experiencing Serious Adverse Events (SAE), Drug-Related Adverse Event (AE), AE Leading to Discontinuation, and Death | AE Leading to Discontinuation | 14 participants |
Secondary
Progression-free Survival, Measured by the Time From Start of Treatment to Progression or Death
Time frame: Baseline to End of study (approximately 48 months)
Population: The study was terminated prior to data collection for this endpoint.
Secondary
Transformation-free Survival Measured by the Time From Start of Treatment to Criteria for Accelerated or Blast Phase CML Are Met and Death
Time frame: Baseline to End of study (approximately 48 months)
Population: The study was terminated prior to data collection for this endpoint.