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

This study has been completed.
Sponsor:
Collaborator:
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

January 13, 2001
April 11, 2013
November 1998
April 2002   (final data collection date for primary outcome measure)
  • 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 ]
Not Provided
Complete list of historical versions of study NCT00008697 on ClinicalTrials.gov Archive Site
  • 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 ]
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Arsenic Trioxide in Treating Patients With Refractory or Recurrent Acute Promyelocytic Leukemia
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Leukemia
Drug: arsenic trioxide
  • 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)

    Intervention: 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)
    Intervention: Drug: arsenic trioxide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
13
April 2002
April 2002   (final data collection date for primary outcome measure)

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.

Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00008697
CDR0000066617, WU-98-0185, NCI-V98-1466
No
Washington University School of Medicine
Washington University School of Medicine
National Cancer Institute (NCI)
Principal Investigator: John F. DiPersio, MD, PhD Washington University School of Medicine
Washington University School of Medicine
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP