Chronic Myelomonocytic Leukemia Clinical Trial
Official title:
PHASE I-II STUDY OF IDARUBICIN, CYTARABINE AND R115777 (TIPIFARNIB, ZARNESTRA; 702818; IND 58359), A FARNESYLTRANSFERASE INHIBITOR, IN PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIAS
This phase I/II trial is studying the side effects and best dose of tipifarnib when given with idarubicin and cytarabine and to see how well it works in treating patients with newly diagnosed myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Tipifarnib (Zarnestra) may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving idarubicin and cytarabine with tipifarnib may kill more cancer cells.
PRIMARY OBJECTIVES:
I. To determine the tolerability of the combination of R115777 (Zarnestra™) and Idarubicin
plus cytarabine by defining the DLT and MTD. (Phase I) II. To determine the efficacy of the
combination of Idarubicin, cytarabine and ZARNESTRA in patients with high-risk MDS and AML.
(Phase II)
OUTLINE: This is a dose-escalation study of tipifarnib. Patients are stratified according to
age (< 50 versus ≥ 50) and, in patients ≥ 50 years of age, cytogenetics (diploid versus
unfavorable).
INDUCTION THERAPY:
PHASE I: Patients receive cytarabine IV continuously on days 1-3 (or 1-4), idarubicin
intravenous (IV) over 1 hour on days 1-3, and oral tipifarnib twice daily on days 1-21.
Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or
unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of tipifarnib 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.
PHASE II: Patients receive cytarabine, idarubicin, and tipifarnib as in phase I at the MTD.
Patients in both phases who respond to induction therapy proceed to consolidation
maintenance therapy.
CONSOLIDATION MAINTENANCE THERAPY: Patients receive consolidation therapy comprising
cytarabine IV continuously on days 1-3, idarubicin IV over 1 hour on days 1-2, and
tipifarnib twice daily on days 1-14. Treatment repeats every 4-6 weeks for 5 courses in the
absence of unacceptable toxicity.
Patients then begin maintenance therapy comprising oral tipifarnib twice daily on day 1-21.
Treatment repeats every 4-6 weeks for 6 courses in the absence of unacceptable toxicity.
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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