Leukemia
Conditions
Brief summary
This study assesses the long-term safety and tolerability of dasatinib administered to patients with chronic myelogenous leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia and experienced clinical benefit from treatment with dasatinib or imatinib in previous protocols.
Interventions
DRUGDasatinib
Dasatinib was supplied as 20- and 50-mg tablets.
DRUGImatinib
Imatinib was supplied as 100- and 400-mg tablets.
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Signed written informed consent * Received treatment in protocols CA180-005, CA180-006, CA180-013, CA180-015 or CA180-017, or CA180-039 * Received clinical benefit with dasatinib or imatinib (study CA180017) in the opinion of the Investigator * Men and women, ages 18 and older Key
Exclusion criteria
* A serious uncontrolled medical disorder or active infection that would impair the ability of the patient to receive protocol therapy * Dementia or altered mental status that would prohibit the understanding or rendering of informed consent * Patients currently taking drugs, including but not limited to quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, ziprasidone, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, and lidoflazine, which are generally accepted to have a risk of causing Torsades de Pointes * Patients taking medications known to be potent CYP3A4 inhibitors (ketoconazole, ritonavir) or inducers (rifampin, efavirenz)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Day 1 of treatment through a maximum of 82 months + 30 days | 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. Related=drug-related; having certain, probable, possible, or unknown relationship to study drug. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Norway, Peru, Poland, Russia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 238 patients were enrolled: 200 with chronic phase chronic myelogenous leukemia (CML) and 38 with advanced phase disease (34 with acclelerated phase CML, 3 with myeloid blast phase CML, and 1 with Philadelphia chromosome positive acute lymphoblastic leukemia.) All but 1 CML patient, who no longer met study criteria, received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib 50 mg QD to 120 mg BID, Chronic Phase Participants with chronic phase disease were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg once daily (QD) to 120 mg twice daily (BID). Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. | 185 |
| Imatinib, 400 mg BID, Chronic Phase Participants with chronic phase disease received 400 mg of imatinib BID. Dose reduction to 600 mg/day (300 mg BID) was permitted, provided the participant had not previously received that dose prior to entry into CA180-017. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. | 14 |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Participants with advanced phase disease, accelerated phase (AP), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. | 34 |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MPB Participants with advanced phase disease, myeloid blast phase (MPB), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. | 3 |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL Participants with advanced phase disease, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. | 1 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 81 | 3 | 11 | 0 | 0 |
| Overall Study | Adverse event unrelated to study drug | 5 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 11 | 0 | 2 | 0 | 0 |
| Overall Study | Disease progression | 30 | 5 | 10 | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Maximum clinical benefit | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Other | 15 | 1 | 3 | 1 | 0 |
| Overall Study | Poor compliance/noncompliance | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Stem cell transplant | 2 | 0 | 0 | 1 | 0 |
| Overall Study | Study drug toxicity | 34 | 1 | 6 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Dasatinib 50 mg QD to 120 mg BID, Chronic Phase | Imatinib, 400 mg BID, Chronic Phase | Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MPB | Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL |
|---|---|---|---|---|---|---|
| Age, Customized 21-45 years | 58 Participants | 46 Participants | 5 Participants | 7 Participants | 0 Participants | 0 Participants |
| Age, Customized 46-65 years | 114 Participants | 88 Participants | 5 Participants | 17 Participants | 3 Participants | 1 Participants |
| Age, Customized 66-75 years | 52 Participants | 40 Participants | 3 Participants | 9 Participants | 0 Participants | 0 Participants |
| Age, Customized Older than 75 years | 13 Participants | 11 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Age, Customized Younger than 21 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 7 Participants | 1 Participants | 6 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 10 Participants | 8 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 206 Participants | 167 Participants | 10 Participants | 26 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 115 Participants | 91 Participants | 6 Participants | 15 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 122 Participants | 94 Participants | 8 Participants | 19 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 138 / 185 | 10 / 14 | 24 / 34 | 2 / 3 | 0 / 1 |
| serious Total, serious adverse events | 57 / 185 | 3 / 14 | 15 / 34 | 1 / 3 | 1 / 1 |
Outcome results
Primary
Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest
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. Related=drug-related; having certain, probable, possible, or unknown relationship to study drug.
Time frame: Day 1 of treatment through a maximum of 82 months + 30 days
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Deaths within 30 days of last dose | 9 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related SAEs | 28 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | SAEs | 57 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs of special interest | 111 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs | 140 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | All deaths | 22 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs leading to discontinuation | 29 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | AEs leading to discontinuation | 39 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs of special interest | 4 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | SAEs | 3 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs | 7 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related SAEs | 2 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs leading to discontinuation | 1 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | All deaths | 0 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Deaths within 30 days of last dose | 0 Participants |
| Imatinib, 400 mg BID, Chronic Phase | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | AEs leading to discontinuation | 1 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related SAEs | 9 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | AEs leading to discontinuation | 10 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs leading to discontinuation | 8 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs of special interest | 20 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs | 27 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | SAEs | 15 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Deaths within 30 days of last dose | 2 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | All deaths | 4 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs of special interest | 1 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Deaths within 30 days of last dose | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | AEs leading to discontinuation | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | All deaths | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | SAEs | 1 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related SAEs | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs leading to discontinuation | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs | 2 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related SAEs | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | SAEs | 1 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Deaths within 30 days of last dose | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs leading to discontinuation | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | All deaths | 0 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | AEs leading to discontinuation | 1 Participants |
| Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL | Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest | Drug-related AEs of special interest | 0 Participants |