Leukemia
Conditions
Keywords
adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (M4), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), untreated adult acute myeloid leukemia
Brief summary
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 cytarabine and daunorubicin, 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 cytarabine and daunorubicin may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given with cytarabine and daunorubicin in treating older patients with acute myeloid leukemia.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin in older patients with previously untreated acute myeloid leukemia. * Determine the toxicity of this regimen in these patients. * Determine the pharmacokinetics of this regimen in these patients. OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Induction therapy (1 course): Patients receive cytarabine IV continuously on days 1-7, daunorubicin IV on days 6-8, and oral tipifarnib twice daily on days 6-15 in the absence of unacceptable toxicity. Patients achieving complete remission proceed to consolidation therapy. Consolidation therapy (1 course): After hematologic recovery, patients begin consolidation therapy 35-60 days after the start of induction therapy. Patients receive cytarabine, daunorubicin, and tipifarnib as in induction therapy. Cohorts of 3-6 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 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 10 patients are treated at the recommended phase II dose. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 3-28 patients will be accrued for this study within 1.5-22 months.
Interventions
DRUGcytarabine
DRUGdaunorubicin hydrochloride
DRUGtipifarnib
Sponsors
National Cancer Institute (NCI)
University Health Network, Toronto
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
56 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of acute myeloid leukemia (AML) * All subtypes, except acute promyelocytic leukemia, are allowed * At least 20% bone marrow or peripheral blood blasts OR biopsy-confirmed extramedullary disease * No cerebrospinal fluid involvement PATIENT CHARACTERISTICS: Age * 56 and over Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * See Disease Characteristics * WBC \< 100,000/mm\^3 (treatment with hydroxyurea allowed) Hepatic * Bilirubin ≤ 1.25 times upper limit of normal (ULN) * AST and ALT ≤ 2.0 times ULN Renal * Creatinine \< 1.7 mg/dL OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * LVEF ≥ 50% * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Immunologic * HIV negative * No history of allergic reaction attributed to compounds of similar chemical or biologic composition to tipifarnib or imidazole drugs (e.g., ketoconazole, clotrimazole, or miconazole) * No ongoing or active infection Other * Not pregnant * Fertile patients must use effective contraception * Able to swallow oral medications * No other uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for AML except hydroxyurea for cytoreduction * More than 4 weeks since prior chemotherapy except hydroxyurea (6 weeks for nitrosoureas or mitomycin) and recovered * At least 24 hours since prior hydroxyurea Endocrine therapy * No concurrent dexamethasone Radiotherapy * More than 4 weeks since prior radiotherapy and recovered * No prior radiotherapy \> 3,000 cGy to marrow-producing areas Surgery * Not specified Other * No other concurrent investigational agents * No other concurrent antileukemic agents * No concurrent treatment with any of the following: * Ketoconazole * Itraconazole * Voriconazole * Clarithromycin * Erythromycin * Phenytoin * Carbamazepine * Barbiturates * Cyclosporine * Pimozide * Warfarin * Grapefruit juice * Simvastatin * Lovastatin * Atorvastatin * No concurrent magnesium- or aluminum-containing antacids within 2 hours before or after tipifarnib administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin | minimum of 30 days per treatment cycle |
| Toxicity | All cycles |
| Pharmacokinetics | Day 6 |
Countries
Canada
Outcome results
None listed