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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00008697
• Other study ID #: CDR0000066617
• Secondary ID: WU-98-0185NCI-V9
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 13, 2001
• Last updated: April 11, 2013
• Start date: November 1998
• Est. completion date: April 2002

Study information

• Verified date: April 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 2002
• Est. primary completion date: April 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Promyelocytic, Acute

Intervention

Drug:
• arsenic trioxide

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) or minimum effective dose (MED)		6 weeks	Yes
Primary	Efficacy (response and survival) at the MTD - Phase 2 only		18 weeks	No
Secondary	Acute and chronic toxicities		18 weeks	Yes
Secondary	Evaluation of the pharmacokinetics and their correlation with toxicities and response		18 weeks	No
Secondary	Evaluation of PML/RARA and PML protein redistribution and degradation following treatment and their correlation with response		18 weeks	No