A Phase I Multicenter Study of Arsenic Trioxide and Azacitidine in Patients With Myelodysplastic Syndromes
- 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
- 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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I)
Every 28 days upto 8 months
Gary J. Schiller, MD
Jonsson Comprehensive Cancer Center
United States: Institutional Review Board
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|