Arsenic Trioxide in Treating Patients With Refractory or Recurrent Acute Promyelocytic Leukemia
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Phase I/II Trial of Infusional Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia|
- Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) or minimum effective dose (MED) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- Efficacy (response and survival) at the MTD - Phase 2 only [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
- Acute and chronic toxicities [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
- Evaluation of the pharmacokinetics and their correlation with toxicities and response [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
- Evaluation of PML/RARA and PML protein redistribution and degradation following treatment and their correlation with response [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||November 1998|
|Study Completion Date:||April 2002|
|Primary Completion Date:||April 2002 (Final data collection date for primary outcome measure)|
Experimental: Phase 1
Cohort 1 Arsenic trioxide = 0.1 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)
Cohort 2 Arsenic trioxide = 0.15 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)
Cohort 3 Arsenic trioxide = 0.20 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)
Cohort 4 Arsenic trioxide = 0.25 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)
Cohort 5 Arsenic trioxide = 0.30 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)
|Drug: arsenic trioxide|
Experimental: Phase 2
Arsenic trioxide = MTD found in Phase 1 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)
|Drug: arsenic trioxide|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00008697
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||John F. DiPersio, MD, PhD||Washington University School of Medicine|