Leukemia
Conditions
Keywords
recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, adult acute promyelocytic leukemia (M3), childhood acute promyelocytic leukemia (M3)
Brief summary
The purpose of this study is to evaluate both the efficacy and toxicity of infusional arsenic trioxide in the treatment of patients with relapsed or refractory acute promyelocytic leukemia (APML). In addition, correlation between pharmacokinetic data and both therapeutic response and therapy-related toxicities will be sought.
Detailed description
OUTLINE: This is a dose-escalation study. Patients receive arsenic trioxide IV over 2 hours daily for 28 days followed by a 14 day rest period. Patients may receive up to 3 courses of treatment. Dose escalation continues in cohorts of 3-6 patients until the maximum tolerated dose (MTD) or minimum effective dose (MED) is determined. The MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity. The MED is defined as the dose at which 4 of 6 patients achieve a complete cytogenetic or molecular response. After the MTD or MED is determined, an additional 20 patients are enrolled at this dose level. Patients are followed monthly for 6 months and every three months for an additional 1.5 years.
Interventions
DRUGarsenic trioxide
Sponsors
National Cancer Institute (NCI)
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. APML diagnosis based upon morphological, histochemical, and/or flow cytometric criteria, confirmed upon review by a central, study-designated hematologic pathologist; OR any relapsed acute leukemia bearing a t(15:17) translocation or variant APML translocations involving the retinoic acid receptor alpha gene on chromosome 15q22, based on cytogenetics or PCR. 2. disease in first or subsequent relapse, following standard induction and consolidation chemotherapy (with all-trans retinoic acid) and/or allogeneic bone marrow/stem cell transplantation; OR failure to achieve initial complete remission with ATRA and standard chemotherapy.
Exclusion criteria
1. Availability of a fully HLA-matched sibling donor for patients otherwise felt to be candidates for allogeneic bone marrow/stem cell transplantation; patients with only a partially HLA-matched sibling or matched unrelated donor will remain eligible for study entry. 2. pregnancy. 3. Patients with significantly impaired left ventricular ejection fraction (\<40%) will be ineligible for the study. Patients with renal failure and a creatinine clearance of less than 25 ml/min or requiring hemodialysis will be ineligible for the study. Otherwise, there are no rigid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) or minimum effective dose (MED) | 6 weeks |
| Efficacy (response and survival) at the MTD - Phase 2 only | 18 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Acute and chronic toxicities | 18 weeks |
| Evaluation of the pharmacokinetics and their correlation with toxicities and response | 18 weeks |
| Evaluation of PML/RARA and PML protein redistribution and degradation following treatment and their correlation with response | 18 weeks |
Countries
United States
Outcome results
None listed