A Phase 1/2 interventional study of cytarabine and idarubicin in Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q) and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), sponsored by City of Hope Medical Center. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-31.
Sponsored by City of Hope Medical Center · Phase 1/2, Interventional, and Treatment
This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patients with acute myeloid leukemia that is likely to come back or spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with cytarabine and idarubicin hydrochloride may be a better treatment for acute myeloid leukemia.
PRIMARY OBJECTIVES:
I. Of the dose levels studied, to determine the maximum tolerated dose of dasatinib when given in combination with cytarabine and idarubicin for treatment of high risk acute myeloid leukemia (AML). (Phase I)
II. To determine the anti-tumor activity of dasatinib when given in combination with cytarabine and idarubicin, as assessed by complete remission rate (CR) and remission duration. (Phase II)
SECONDARY OBJECTIVES:
I. To document CR and survival outcomes (overall, event-free). (Phase I)
II. To estimate the survival probabilities (overall and event-free) and cumulative incidence of relapse/progression. (Phase II)
III. To describe and summarize all toxicities by organ and severity. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of dasatinib, followed by a phase II study.
Patients receive cytarabine intravenously (IV) continuously over 168 hours on days 1-7, dasatinib orally (PO) once daily (QD) on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 2 months for up to 2 years.
993 studies on the registry are indexed under Congenital Abnormalities; 174 are open to participants now.
This study's enrollment of 20 is below the median of 49 across 499 interventional studies indexed under Congenital Abnormalities.
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Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.
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Patients diagnosed with AML meeting one of the following criteria:
Any prior chemotherapy must have been completed >= 2 weeks prior to day 1 of study treatment and the participant must have recovered to eligibility levels from prior toxicity
Only one prior regimen is allowed for relapsed AML patients; note one prior regimen is defined as follows:
Exclusion Criteria:
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
Drug: cytarabine · Drug: idarubicin · Drug: dasatinib · Other: laboratory biomarker analysis
Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.
Drug: cytarabine · Drug: idarubicin · Drug: dasatinib · Other: laboratory biomarker analysis
Given IV
Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Given IV
Also known as: 4-demethoxydaunorubicin, 4-DMDR, DMDR, IDA
Given PO
Also known as: BMS-354825, Sprycel
Correlative studies
Maximum Tolerated Dose of Dasatinib (Phase I)
Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Time frame: From the first dose of Dasatinib through the DLT observation period (Day +28)
Complete Remission Rate (Phase II)
Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.
Time frame: From the first cycle up to two years
Overall Survival (Phase II)
Overall survival was measured from the first dose of Dasatinib to death from any cause or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
Time frame: Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years
Event-free Survival (Phase II)
Event-free survival was defined as time from the first dose of Dasatinib to relapse/progression, receipt of anti-leukemia therapy, death, or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
Time frame: Time from start of study therapy until death, relapse/progression, receipt of anti-leukemia therapy, or last contact, whichever comes first, assessed up to two years.
Due to the funding issue, the study was stopped early before reaching the target accrual. However, all the enrolled patients had received the treatment drug per protocol.
| Milestone | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day |
|---|---|---|
| Started | 17 | 3 |
| Completed | 17 | 3 |
| Not completed | 0 | 0 |
Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
| mg/m2 | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day |
|---|---|
| Maximum Tolerated Dose of Dasatinib (Phase I) | 100 |
Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.
No measurements were reported for this outcome.
Overall survival was measured from the first dose of Dasatinib to death from any cause or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
No measurements were reported for this outcome.
Event-free survival was defined as time from the first dose of Dasatinib to relapse/progression, receipt of anti-leukemia therapy, death, or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
No measurements were reported for this outcome.
Collected over Adverse event and vital status data were captured from the initial treatment to off study, up to 2 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | 11/17 (64.7%) | 4/17 (23.5%) | 17/17 (100%) |
| Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | 3/3 (100%) | 0/3 (0%) | 3/3 (100%) |
| Event | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day |
|---|---|---|
| Death NOSGeneral disorders | 1/17 | 0/3 |
| Multi-organ failureGeneral disorders | 1/17 | 0/3 |
| Intracranial hemorrhageNervous system disorders | 1/17 | 0/3 |
| Adult respiratory distress syndromeRespiratory, thoracic and mediastinal disorders | 1/17 | 0/3 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/17 | 0/3 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 1/17 | 0/3 |
| Event | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day |
|---|---|---|
| 10002272-AnemiaBlood and lymphatic system disorders | 16/17 | 3/3 |
| 10012727-DiarrheaGastrointestinal disorders | 12/17 | 3/3 |
| 10028813-NauseaGastrointestinal disorders | 13/17 | 3/3 |
| 10016256-FatigueGeneral disorders | 10/17 | 3/3 |
| 10050068-Edema limbsGeneral disorders | 9/17 | 3/3 |
| 10005364-Blood bilirubin increasedInvestigations | 11/17 | 3/3 |
| 10025256-Lymphocyte count decreasedInvestigations | 15/17 | 3/3 |
| 10029366-Neutrophil count decreasedInvestigations | 12/17 | 3/3 |
| 10035528-Platelet count decreasedInvestigations | 17/17 | 3/3 |
| 10020943-HypoalbuminemiaMetabolism and nutrition disorders | 13/17 | 3/3 |
| Age, Continuous(years) | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Total |
|---|---|---|---|
| Median | 62 (27 to 73) | 63 (52 to 69) | 63 (27 to 73) |
| Sex: Female, Male(Participants) | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Total |
|---|---|---|---|
| Female | 4 | 1 | 5 |
| Male | 13 | 2 | 15 |
| Ethnicity (NIH/OMB)(Participants) | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 2 |
| Not Hispanic or Latino | 15 | 3 | 18 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 3 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 12 | 1 | 13 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(Participants) | Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day | Total |
|---|---|---|---|
| United States | 17 | 3 | 20 |
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Studies of the drugs tested here: Cytarabine · Idarubicin · Dasatinib