RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with etoposide may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib and etoposide in treating older patients with newly diagnosed acute myeloid leukemia.

Condition	Treatment or Intervention	Phase
adult acute erythroid leukemia adult acute monoblastic and acute monocytic leukemia adult acute myeloid leukemia secondary acute myeloid leukemia	Drug: etoposide  Drug: tipifarnib  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the feasibility, tolerability, and toxic effects of tipifarnib and etoposide in older patients with newly diagnosed, previously untreated acute myeloid leukemia.
• Determine the maximum tolerated dose of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral tipifarnib twice daily on days 1-14 OR 1-21 and oral etoposide once daily on days 1-3 and 8-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) may receive up to 5 additional courses of therapy beyond documentation of CR.

Cohorts of 3-6 patients receive escalating doses of tipifarnib and etoposide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 14 additional patients receive treatment at the MTD.

After completion of study treatment, patients are followed at 1 month and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 3-100 patients will be accrued for this study.

Ages Eligible for Study:  70 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed acute myeloid leukemia (AML), including the following subtypes:
• M0
• M1
• M2
• M4
• M5
• M6
• M7
• Newly diagnosed de novo or secondary (myelodysplastic syndrome [MDS]-related or treatment-related) AML
• No hyperleukocytosis (i.e., ≥ 30,000 blasts/μL or rapidly rising blast count with projected doubling time of ≤ 2 days)
• No acute promyelocytic leukemia (M3)
• No active CNS leukemia

PATIENT CHARACTERISTICS: Age

• 70 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• SGOT and SGPT ≤ 5 times upper limit of normal
• Bilirubin ≤ 2.0 mg/dL

Renal

• Creatinine ≤ 2.0 mg/dL

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active uncontrolled infection
• Infection under active treatment and controlled with antibiotics allowed
• No other life-threatening illness
• No mental deficit and/or psychiatric history that would preclude giving informed consent or study participation
• No allergy to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior thalidomide, interferon, or cytokines for MDS allowed
• No concurrent immunotherapy

Chemotherapy

• Prior hydroxyurea allowed
• Prior azacytidine for MDS allowed
• No prior etoposide
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• Other prior noncytotoxic therapy for MDS allowed
• No prior tipifarnib
• No concurrent antacids (magnesium- or aluminum-containing formulations) within 2 hours before or after study drug administration
• No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, or oxcarbazepine)

Please refer to this study by ClinicalTrials.gov identifier  NCT00112853

Florida
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612,  United States; Recruiting
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
New York
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000428305; JHOC-05020806; NCI-6954
Record last reviewed:  May 2005
Last Updated:  June 2, 2005
Record first received:  June 2, 2005
ClinicalTrials.gov Identifier:  NCT00112853
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-06-07