Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes
RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with arsenic trioxide and to see how well they work in treating patients with myelodysplastic syndromes.
|Leukemia Myelodysplastic Syndromes||Drug: arsenic trioxide Drug: azacitidine||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I Multicenter Study of Arsenic Trioxide and Azacitidine in Patients With Myelodysplastic Syndromes|
- Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I) [ Time Frame: Every 28 days upto 8 months ]
- Time to disease progression [ Time Frame: Participants are folowed for an average of 1 year after completion of study treatment ]
- Overall survival [ Time Frame: Participants are followed every 3-12 months for survival ]
|Study Start Date:||February 2007|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
see description in intervention
Drug: arsenic trioxide
Each 28-day treatment cycle will include dosing for 2 days per week of ATO. Subjects will recieve 1 mg/mL each dosing day.
Other Name: ATODrug: azacitidine
Each 28-day treatment cycle will include dosing the first five days of cycle with Azacitidine. Cohorts of three to six patients will each receive 25, 50, and 75 mg/m2/d injected subcutaneously.
- Determine the maximum tolerated dose of azacitidine when given in combination with arsenic trioxide in patients with myelodysplastic syndromes (MDS). (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase I)
- Determine the major hematologic response (erythroid response) rate in patients with transfusion-dependent lower-risk MDS treated with this regimen. (Phase II)
- Determine complete and partial remission rates in patients with higher-risk MDS treated with this regimen. (Phase II)
- Determine the toxicity profile of this regimen in these patients. (Phase I)
- Determine time to disease progression in patients treated with this regimen. (Phase I and II)
- Determine the overall and progression-free survival of patients treated with this regimen. (Phase I and II)
OUTLINE: This is an multicenter, open-label, phase I, dose escalation study of azacitidine followed by a phase II study. Patients enrolled in the phase II portion are stratified according to baseline International Scoring System score (lower-risk myelodysplastic syndromes [MDS] vs higher-risk MDS).
- Phase I: Patients receive azacitidine subcutaneously once daily on days 1-5 and arsenic trioxide IV over 1-4 hours on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease may receive up to 8 courses of therapy. Patients with responding disease may continue to receive study therapy until a major response or a complete remission is achieved.
Cohorts of 3-6 patients receive escalating doses of azacitidine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive arsenic trioxide as in phase I and azacitidine as in phase I at one dose level below the MTD determined in phase I.
After the completion of study treatment, patients are followed at 4 weeks and then every 3-12 months for survival.
PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 60 patients (30 per stratum) will be accrued for the phase II portion of this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00234000
|United States, California|
|Jonsson Comprehensive Cancer Center at UCLA|
|Los Angeles, California, United States, 90095-1781|
|Principal Investigator:||Gary J. Schiller, MD||Jonsson Comprehensive Cancer Center|