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

NCT ID: NCT00008697

Last Updated: 2013-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-11-30
• Study Completion Date: 2002-04-30

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.

Conditions

Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Study Groups

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)

Group Type: EXPERIMENTAL

arsenic trioxide

Intervention Type: DRUG

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)

Group Type: EXPERIMENTAL

arsenic trioxide

Intervention Type: DRUG

Interventions

arsenic trioxide

Intervention Type: DRUG

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John F. DiPersio, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Other Identifiers

WU-98-0185

Identifier Type: -

Identifier Source: secondary_id

NCI-V98-1466

Identifier Type: -

Identifier Source: secondary_id

CDR0000066617

Identifier Type: -

Identifier Source: org_study_id