A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)
Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)
About this trial
This is an interventional treatment trial for Adult Acute Myeloid Leukemia in Remission
Eligibility Criteria
Inclusion Criteria: Pathological Confirmation of the Diagnosis of AML, MDS PMNs >= 1,000/ul Platelets >= 30,000/ul Hematocrit >= 27% and/or Hemoglobin >= 9 gm/dl unsupported ECOG Performance Status 0-2 Patients must be able to give informed consent Female patients of childbearing age must have negative pregnancy test AST, ALT and Alkaline Phosphatase =<2.5 x normal Bilirubin =< 1.5 x normal Serum Creatinine =< 2.0 mg/dl or Creatinine Clearance >= 40 ml/min Left Ventricular Ejection Fraction >= 25% Patients with poor-risk AML or high-risk MDS who have completed both induction and consolidation chemotherapy; poor risk AML is defined by one or more of the following characteristics: Antecedent Hematologic Disorder AML Arising from MDS Therapy-related AML Age >= 60 (in absence of favorable cytogenetics) Adverse Cytogenetics (i.e., -5/5q, -7/7q, +8, 20q-, 11q23 abnormalities, complex karyotype; other abnormalities may be considered at discression of study chair) Hyperleukocytosis at diagnosis (Blasts >= 30,000/mm^3 at diagnosis in absence of favorable cytogenetics) High Risk MDS is defined by one or more of the following characteristics: RAEB and RAEB-t, with IPSS Score >= 1.5 (adverse cytogenetics, > 10% marrow blasts, cytopenias in at least 2 lineages): See Appendix E (Greenberg, et al. Blood 89:2079-2088,1997)36 CMML with > 5% marrow blasts Therapy-related MDS Exclusion Criteria: Any previous treatment with ZARNESTRA Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial) Acute promyelocytic (FAB M3) subtype Presence of (8;21) translocation or inversion 16 genotype as sole abnormality Eligible for curative allogeneic stem cell transplantation Known allergy to imidazole drugs (e.g., ketoconazole, miconazole) Presence of Residual AML (> 5% marrow blasts) or MDS, as Determined by Morphology, Flow Cytometry, and/or Cytogenetics Active, Uncontrolled Infection Disseminated Intravascular Coagulation Active CNS Leukemia Concomitant Chemotherapy, Radiation Therapy or Immunotherapy Women who are pregnant or lactating will not be eligible for this trial, as the investigational agent may be harmful to the developing fetus or nursing infant
Sites / Locations
- Johns Hopkins University
Arms of the Study
Arm 1
Experimental
Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.