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

April 11, 2013 updated by: Washington University School of Medicine

A Phase I/II Trial of Infusional Arsenic Trioxide for Relapsed 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 Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) or minimum effective dose (MED)
Time Frame: 6 weeks
6 weeks
Efficacy (response and survival) at the MTD - Phase 2 only
Time Frame: 18 weeks
18 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Acute and chronic toxicities
Time Frame: 18 weeks
18 weeks
Evaluation of the pharmacokinetics and their correlation with toxicities and response
Time Frame: 18 weeks
18 weeks
Evaluation of PML/RARA and PML protein redistribution and degradation following treatment and their correlation with response
Time Frame: 18 weeks
18 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: John F. DiPersio, MD, PhD, Washington University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1998

Primary Completion (Actual)

April 1, 2002

Study Completion (Actual)

April 1, 2002

Study Registration Dates

First Submitted

January 13, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

April 12, 2013

Last Update Submitted That Met QC Criteria

April 11, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000066617
  • WU-98-0185
  • NCI-V98-1466

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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