Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission

PRIMARY OBJECTIVES:

I. To compare R115777 (tipifarnib) maintenance therapy to observation only with respect to disease-free survival (DFS) in patients with AML in second or subsequent complete remission or in complete response (CR) following primary induction failure.

SECONDARY OBJECTIVES:

I. To compare overall survival of patients in both arms. II. To evaluate the long-term safety and toxicity of extended administration of R115777 in AML patients in remission.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo observation only.

After completion of study treatment, patients are followed up for 5 years.

Inclusion criteria

• Patients eligible to enter this study must fall into one of these categories:

• Patients in first remission following primary induction failure
• Patients must have received at least two chemotherapy induction regimens
• Patients in second or subsequent remission
• Patients > 60 years old in first remission
• Patients must be in complete remission (CR) or morphologic remission (MR) by blood counts and bone marrow studies to enter the study

• Confirmatory bone marrow must be performed =< 2 weeks prior to randomization
• Patients must have morphologic proof (from bone marrow aspirate, smears or touch preps of marrow biopsy) that they had AML of one of the following types prior to achievement of CR/MR

• Acute myeloblastic leukemia, minimal differentiation (French-American-British [FAB] M0)
• Acute myeloblastic leukemia without differentiation (FAB M1)
• Acute myeloblastic leukemia with maturation (FAB M2)
• Acute myelomonocytic leukemia (FAB M4)
• Acute monocytic leukemia (FAB M5)
• Acute erythroleukemia (FAB M6)
• Acute megakaryocytic leukemia (FAB M7)
• Refractory anemia with excess blasts in transformation (RAEB-T)
• AML by World Health Organization (WHO) criteria
• Acute myeloid leukemia with multilineage dysplasia
• Patients with acute promyelocytic leukemia (FAB M3) are not eligible
• Patients must be registered within 60 days of completion of therapy for the current remission; patients are eligible if they meet any of the criteria below:

• Within 60 days of remission (CR or MR) by peripheral blood counts following induction therapy or
• Within 60 days of discharge from the hospital following induction therapy or
• Within 60 days of discharge from the hospital following post-remission therapy or
• Within 60 days of recovery of blood counts following last dose of chemotherapy
• All of the patients below are eligible for study entry:

• Patients who have received consolidation therapy
• Patients who have not received any consolidation or post remission therapy
• Patients who have had an autologous stem cell transplant
• Patients who have received an allogeneic transplant (bone marrow transplant [BMT] or peripheral stem cell transplant [PSCT]) in their current remission are ineligible; patients who have had an allogeneic transplant in a previous remission and are currently in remission after subsequent relapse are eligible
• Patients with a history of extramedullary disease are eligible if they are in complete remission at the time of study entry and no longer requiring therapy for their extramedullary disease
• Patients must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study < 2 weeks prior to randomization to rule out pregnancy
• Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
• Patients must not be known to have an allergy to imidazole drugs, such as clotrimazole ketoconazole, miconazole, econazole, or terconazole; this does not include fluconazole, voriconazole, or itraconazole
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
• Patients must not have active cardiac or pulmonary disease; but patient will be eligible if disease is medically controlled
• Patients must not have active renal disease; creatinine must be =< 1.5 x upper limit of normal
• Patients must not have active hepatic disease; total or direct bilirubin must be < 2 mg/dl
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) must be =< 2.5 times the upper limit of normal
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 50,000/mm^3
• Patients must not be taking a hepatic enzyme-inducing anti-convulsant; a patient will not be eligible for the study if the patient is currently taking one of these agents and cannot be switched to a non-hepatic enzyme-inducing anti-convulsant