RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating patients who have acute myeloid leukemia or myelodysplastic syndrome in first complete remission.

Condition	Treatment or Intervention	Phase
adult acute monoblastic and acute monocytic leukemia adult acute myeloid leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndromes	Drug: tipifarnib  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the duration of disease-free survival and overall survival of patients with poor-risk acute myeloid leukemia or high-risk myelodysplastic syndromes in early first complete remission treated with tipifarnib.
• Determine the tolerability and toxic effects of this drug in these patients.

OUTLINE: This is a multicenter study.

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.

PROJECTED ACCRUAL: A total of 14-44 patients will be accrued for this study within 11-15 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:
• Poor-risk acute myeloid leukemia (AML), defined as any of the following:
• Antecedent hematologic disorder
• AML arising from myelodysplastic syndromes (MDS)
• Therapy-related AML
• 60 years of age or over (in absence of favorable cytogenetics)
• Adverse cytogenetics (e.g., -5/5q, -7/7q, 20q-, or 11q23 abnormalities or complex karyotype)
• Hyperleukocytosis at diagnosis (e.g., blasts at least 50,000/mm^3 in absence of favorable cytogenetics)
• No acute promyelocytic leukemia (FAB M3 subtype)
• High-risk myelodysplastic syndromes (MDS), defined as any of the following:
• Chronic myelomonocytic leukemia with more than 5% marrow blasts
• Therapy-related MDS
• Refractory anemia with excess blasts (RAEB) with IPSS score at least 1.5
• RAEB in transformation with IPSS score at least 1.5
• In early first complete remission after completing induction and consolidation chemotherapy
• No more than 21-35 days since hospital discharge after marrow recovery from consolidation therapy
• No more than 120 days since initiation of the final course of consolidation therapy
• No presence of residual AML (more than 5% marrow blasts) or MDS by morphology, flow cytometry, and/or cytogenetics
• No active CNS leukemia
• No presence of (8;21) translocation or inversion 16 genotype as sole abnormality
• Ineligible for curative allogeneic stem cell transplantation

PATIENT CHARACTERISTICS: Age

• See Disease Characteristics
• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Polymorphonuclear cell count at least 1,000/mm^3
• Platelet count at least 30,000/mm^3*
• Hemoglobin at least 9 g/dL*
• Hematocrit at least 27%* NOTE: *Unsupported

Hepatic

• Bilirubin no greater than 1.5 times normal
• AST and ALT no greater than 2.5 times normal
• Alkaline phosphatase no greater than 2.5 times normal

Renal

• Creatinine no greater than 2.0 mg/dL OR
• Creatinine clearance at least 40 mL/min

Cardiovascular

• No disseminated intravascular coagulation
• LVEF at least 25%

Other

• No active uncontrolled infection
• No known allergy to imidazole drugs (e.g., ketoconazole or miconazole)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior tipifarnib
• No concurrent participation in another phase II or phase III study in which disease-free survival and overall survival are primary endpoints

Georgia
      Blood and Marrow Transplant Group of Georgia, Atlanta,  Georgia,  30342-4777,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
New York
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting

Study chairs or principal investigators

Judith E. Karp, MD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000256885; JHOC-J0252; MSGCC-0150; NCI-5689; NCT00045396
Record last reviewed:  February 2005
Last Updated:  February 24, 2005
Record first received:  September 6, 2002
ClinicalTrials.gov Identifier:  NCT00045396
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08