Arsenic Trioxide With or Without Tretinoin in Treating Patients With Hematologic Cancer That Has Not Responded to Previous Therapy
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.
Multiple Myeloma and Plasma Cell Neoplasm
Drug: arsenic trioxide
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Arsenic Trioxide Alone or With ATRA (Vesanoid) for Resistant Hematologic Malignancy|
- Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
- Likelihood of complete (CR) or partial (PR) response following therapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Explore the pharmacokinetics of arsenic trioxide alone and in combination with ATRA [ Designated as safety issue: No ]
- Evaluate acute and chronic toxicities of arsenic trioxide alone and in combination with ATRA. [ Designated as safety issue: Yes ]
- 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 [ Designated as safety issue: No ]Only when patients are circulating tumor cells.
|Study Start Date:||June 1999|
|Study Completion Date:||February 2002|
|Primary Completion Date:||November 2000 (Final data collection date for primary outcome measure)|
Experimental: Phase I
Starting dose of arsenic trioxide of 0.15 mg/kg/day
|Drug: arsenic trioxide|
Experimental: Phase II
MTD of arsenic trioxide
|Drug: arsenic trioxide|
Experimental: Treatment Failure
Arsenic trioxide and tretinoin
|Drug: arsenic trioxide Drug: tretinoin|
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.
|United States, Missouri|
|Washington University Barnard Cancer Center|
|Saint Louis, Missouri, United States, 63110|
|Study Chair:||Randy A. Brown, MD||Washington University Siteman Cancer Center|