A Phase I/II Trial of Infusional Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia

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

Sponsors

Lead sponsor: Washington University School of Medicine

Collaborator: National Cancer Institute (NCI)

Source 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.

Overall Status Completed
Start Date November 1998
Completion Date April 2002
Primary Completion Date April 2002
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
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 Outcome
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
Enrollment 13
Condition
Intervention

Intervention type: Drug

Intervention name: arsenic trioxide

Eligibility

Criteria:

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 exclusion criteria based upon age, performance status, or co-morbidity. Decisions regarding enrollment of patients for whom these factors may be relevant will be individualized and left to the discretion of the investigators. Central venous access will be required for all patients. Patients of child-bearing potential must agree to use contraception during sexual intercourse while undergoing treatment with arsenic trioxide.

Gender: All

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
John F. DiPersio, MD, PhD Principal Investigator Washington University School of Medicine
Location
facility Washington University School of Medicine
Location Countries

United States

Verification Date

April 2013

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Phase 1

Arm group type: Experimental

Description: 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)

Arm group label: Phase 2

Arm group type: Experimental

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

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Source: ClinicalTrials.gov