Arsenic Trioxide With or Without Tretinoin in Treating Patients With Hematologic Cancer That Has Not Responded to Previous Therapy

Phase 1

Terminated

• Conditions: Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
• Interventions: Drug: arsenic trioxide; Drug: tretinoin

• Registration Number: NCT00006220
• Lead Sponsor: Washington University School of Medicine

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Tretinoin may help hematologic cancer cells develop into normal white blood cells.

PURPOSE: Phase I/II trial to study the effectiveness of arsenic trioxide with or without tretinoin in treating patients who have hematologic cancer that has not responded to previous therapy.

Detailed Description

This is a dose escalation and efficacy study of arsenic trioxide. In the efficacy study, patients are stratified according to diagnosis (acute myelogenous leukemia vs acute lymphocytic leukemia vs myelodysplastic syndrome vs multiple myeloma vs non-Hodgkin's lymphoma and Hodgkin's disease). Phase I: Patients receive arsenic trioxide IV over 2 hours daily for 28 days. Treatment repeats every 42-59 days in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) or partial remission (PR) receive up to 4 courses. Patients who fail to achieve CR or PR or who experience disease progression may receive arsenic trioxide and tretinoin daily for 28 days every 42-59 days for up to 7 courses. Patients who fail to achieve CR or PR or experience disease progression with arsenic trioxide and tretinoin are removed from study. Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. Phase II: Patients receive the MTD of arsenic trioxide as in phase I for up to 7 courses. Patients who fail to achieve CR or PR after 3 courses or experience disease progression are either taken off study or treated with arsenic trioxide and tretinoin as in phase I. Patients are followed monthly for 6 months, and then every 3 months for 18 months.

Study Timeline

• Study Start: 1999-06
• Study First Submitted: 2000-09-11
• Primary Completion: 2000-11
• Study Completion: 2002-02
• Study First Submitted QC: 2004-05-19
• Study First Posted: 2004-05-20
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-04
• Last Update Posted: 2013-02-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase I	arsenic trioxide	Starting dose of arsenic trioxide of 0.15 mg/kg/day
Treatment Failure	tretinoin	Arsenic trioxide and tretinoin
Phase II	arsenic trioxide	MTD of arsenic trioxide
Treatment Failure	arsenic trioxide	Arsenic trioxide and tretinoin

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT)	28 days
Likelihood of complete (CR) or partial (PR) response following therapy	6 months

Secondary Outcome Measures

Name	Time	Method
Explore the pharmacokinetics of arsenic trioxide alone and in combination with ATRA
Evaluate acute and chronic toxicities of arsenic trioxide alone and in combination with ATRA.
Determine the effects of arsenic trioxide alone and combined with ATRA on bcl-2, pml, and class I antigen expression and on apoptosis. Determine the effects of arsenic trioxide on T and B cell number and function		Only when patients are circulating tumor cells.

Trial Locations

Locations (1)

Washington University Barnard Cancer Center; 🇺🇸 Saint Louis, Missouri, United States