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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00008697
First received: January 13, 2001
Last updated: April 11, 2013
Last verified: April 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Leukemia
 Drug: arsenic trioxide
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Infusional Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) or minimum effective dose (MED) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Efficacy (response and survival) at the MTD - Phase 2 only [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute and chronic toxicities [ Time Frame: 18 weeks ] [ Designated as safety issue: Yes ]
  • Evaluation of the pharmacokinetics and their correlation with toxicities and response [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Evaluation of PML/RARA and PML protein redistribution and degradation following treatment and their correlation with response [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: November 1998
Study Completion Date: April 2002
Primary Completion Date: April 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00008697

Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
National Cancer Institute (NCI)
Investigators
Principal Investigator: John F. DiPersio, MD, PhD Washington University School of Medicine
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00008697     History of Changes
Other Study ID Numbers: CDR0000066617, WU-98-0185, NCI-V98-1466
Study First Received: January 13, 2001
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
adult acute promyelocytic leukemia (M3)
childhood acute promyelocytic leukemia (M3)

Additional relevant MeSH terms:
Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
 Leukemia, Myeloid
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013