Arsenic Trioxide in Treating Patients With Refractory or Recurrent Acute Promyelocytic Leukemia

Phase 1

Completed

• Conditions: Leukemia
• Interventions: Drug: arsenic trioxide

• Registration Number: NCT00008697
• Lead Sponsor: Washington University School of Medicine

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.

Study Timeline

• Study Start: 1998-11
• Study First Submitted: 2001-01-13
• Primary Completion: 2002-04
• Study Completion: 2002-04
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-11
• Last Update Posted: 2013-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1	arsenic trioxide	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)
Phase 2	arsenic trioxide	Arsenic trioxide = MTD found in Phase 1 mg/kg/day x 28 days with 14 day rest for 3 cycles (each cycle = 6 weeks)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States