A Phase I Trial Of Sequential Administration Of Triapine (3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone) Followed By Fludarabine In Adults With Relapsed And Refractory Leukemias And Myelodysplasias
- Determine the feasibility and tolerability of 3-AP (Triapine^® ) followed by
fludarabine in patients with relapsed or refractory acute or chronic leukemia or
high-risk myelodysplastic syndromes.
- Determine the toxic effects of this regimen in these patients.
- Determine the maximum tolerated dose of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are
stratified according to disease (acute leukemias and myelodysplastic syndromes [MDS] vs
chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2
- Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive
3-AP (Triapine^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5.
Cohorts of 3-6 patients receive escalating doses of fludarabine 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 toxicity. Once the MTD is determined, 10 additional
patients are treated at that dose level.
- Group 2 (acute leukemias or MDS): Patients receive 3-AP IV continuously over 24 hours
on day 1. Beginning within 4 hours after completion of 3-AP, patients receive
fludarabine IV over 30 minutes on days 2-6.
In both groups, treatment repeats every 3 weeks in the absence of disease progression or
PROJECTED ACCRUAL: A total of 3-34 patients will be accrued for this study.
Primary Purpose: Treatment
Judith E. Karp, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|M.D. Anderson Cancer Center at University of Texas||Houston, Texas 77030|
|Greenebaum Cancer Center at University of Maryland Medical Center||Baltimore, Maryland 21201|
|Blood and Marrow Transplant Group of Georgia||Atlanta, Georgia 30342-1601|