Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

NCT ID: NCT00101153

Last Updated: 2015-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30

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.

Conditions

Leukemia

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tipifarnib with conventional induction and consolidation

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

tipifarnib

Intervention Type: DRUG

Interventions

cytarabine

Intervention Type: DRUG

daunorubicin hydrochloride

Intervention Type: DRUG

tipifarnib

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 56 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Brandwein, MD

Role: STUDY_CHAIR

Princess Margaret Hospital, Canada

Locations

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada

Countries

Canada

References

Brandwein JM, Leber BF, Howson-Jan K, Schimmer AD, Schuh AC, Gupta V, Yee KW, Wright J, Moore M, MacAlpine K, Minden MD; NCI CTEP Protocol 6670. A phase I study of tipifarnib combined with conventional induction and consolidation therapy for previously untreated patients with acute myeloid leukemia aged 60 years and over. Leukemia. 2009 Apr;23(4):631-4. doi: 10.1038/leu.2008.341. Epub 2008 Dec 18.

Reference Type: RESULT

PMID: 19092853 (View on PubMed)

Other Identifiers

CDR0000405840

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-6670

Identifier Type: -

Identifier Source: secondary_id

PMH-PHL-026

Identifier Type: -

Identifier Source: org_study_id