RATIONALE: 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 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.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
adult acute erythroid leukemia adult acute monoblastic and acute monocytic leukemia adult acute myeloid leukemia childhood acute myeloid leukemia and other myeloid malignancies Chronic Myelomonocytic Leukemia secondary acute myeloid leukemia	Drug: cytarabine  Drug: idarubicin  Drug: tipifarnib  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of tipifarnib when administered with idarubicin and cytarabine in patients with newly diagnosed high-risk myelodysplastic syndromes or acute myeloid leukemia. (Phase I)
• Determine the tolerability of this regimen in these patients. (Phase I)
• Determine the efficacy of this regimen in these patients. (Phase II)

OUTLINE: This is a dose-escalation study of tipifarnib. Patients are stratified according to age (< 50 vs ≥ 50) and, in patients ≥ 50 years of age, cytogenetics (diploid vs unfavorable).

• Patients receive cytarabine IV continuously on days 1-3 (or 1-4), idarubicin 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.
• 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.

PROJECTED ACCRUAL: Approximately 6-96 patients (at least 6 for phase I and 90 for phase II) will be accrued for this study within 1 year.

Ages Eligible for Study:  15 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:
• Acute myeloid leukemia (AML) (WHO classification definition of ≥ 20% blasts)
• High-risk myelodysplastic syndromes (MDS) defined as the presence of ≥ 10% blasts
• Newly diagnosed disease
• No acute promyelocytic leukemia

PATIENT CHARACTERISTICS: Age

• 15 to 70

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 2 mg/dL (unless increase is due to hemolysis)
• SGPT ≤ 2.5 times upper limit of normal

Renal

• Creatinine ≤ 2 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take oral medication
• No active systemic infection
• No known allergy to imidazole drugs, including the following:
• Clotrimazole
• Ketoconazole
• Miconazole
• Econazole
• Fenticonazole
• Isoconazole
• Sulconazole
• Tioconazole
• Terconazole
• No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior hematopoietic growth factors allowed
• Prior transfusion or apheresis allowed

Chemotherapy

• No prior chemotherapy (except hydroxyurea [0.5-5 g/day for up to 3 days]) for AML or MDS

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• Prior vitamins allowed
• Concurrent antacids (magnesium or aluminum-containing products) allowed provided they are administered at least 2 hours before or 2 hours after tipifarnib administration
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, or carbamazepine)
• No other concurrent therapy for MDS, including systemic retinoids
• No other concurrent anticancer therapy

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Hagop M. Kantarjian, MD,  Study Chair,  M.D. Anderson Cancer Center   
Jorge Cortes, MD,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000391190; MDA-2003-0563; NCI-6625; NCT00096122
Record last reviewed:  October 2004
Last Updated:  February 24, 2005
Record first received:  November 9, 2004
ClinicalTrials.gov Identifier:  NCT00096122
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08