Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 70 and over NCI SWOG-S0432 S0432, CALGB-SWOG-S0432, ECOG-SWOG-S0432, NCT00093418

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. Determine the efficacy of 4 different regimens of tipifarnib in older patients with previously untreated acute myeloid leukemia.
2. Provide increased access to this drug for these patients.
3. Determine the frequency and severity of toxic effects of these regimens in these patients.
4. Correlate, preliminarily, response to this drug with cytogenetics and assess whether karyotype represents a potential prognostic factor in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Morphologically confirmed acute myeloid leukemia (AML) by bone marrow aspiration and biopsy
  • No acute promyelocytic leukemia (FAB M3) or blastic transformation of chronic myelogenous leukemia



• Ineligible for or refused standard AML cytotoxic chemotherapy regimens



• Prior myelodysplastic syndromes (MDS) allowed



• Concurrent enrollment on SWOG-9007 (cytogenetics protocol) required (Southwest Oncology Group patients only)

Prior/Concurrent Therapy:

Biologic therapy

• Prior hematopoietic growth factors, thalidomide, or signal transduction inhibitors for MDS allowed
• Concurrent growth factors for MDS allowed

Chemotherapy

• No prior systemic chemotherapy for acute leukemia except hydroxyurea
• No prior AML induction type chemotherapy or high-dose chemotherapy with hematopoietic stem cell support for MDS
• Prior arsenic trioxide, azacitidine, or low-dose (< 100 mg/m²/day) cytarabine for MDS allowed
• At least 6 months since chemotherapy for a prior malignancy

Endocrine therapy

• Concurrent hormonal therapy allowed

Radiotherapy

• At least 6 months since radiotherapy for a prior malignancy

Surgery

• Not specified

Other

• Recovered from all prior therapy
• Other prior low-intensity therapy for MDS allowed
• No concurrent therapy for MDS (other than growth factors)
• No antacids within 2 hours of tipifarnib administration
• No concurrent enzyme-inducing anticonvulsants, including phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, and oxcarbazepine

Patient Characteristics:

Age

• 70 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≤ 30,000/mm³ (hydroxyurea allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (except when attributed to Gilbert's syndrome or hemolysis)
• AST or ALT ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Other

• Fertile patients must use effective contraception
• Prior malignancy allowed

Expected Enrollment

A total of 60-296 patients (15-74 per treatment arm) will be accrued for this study.

Outcomes

Efficacy
Drug availability
Frequency and severity of toxic effects
Correlation of response with cytogenetics

Outline

This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral tipifarnib twice daily on days 1-21.



• Arm II: Patients receive oral tipifarnib twice daily on days 1-7 and 15-21.



• Arm III: Patients receive tipifarnib as in arm I, but at a lower dose.



• Arm IV: Patients receive tipifarnib as in arm II, but at a lower dose.

In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

Erba HP, Kopecky KJ, Kirschbaum MH, et al.: Phase II studies of different schedules and doses of the farnesyl transferase inhibitor tipifarnib (R115777, zarnestra, NSC-702818) for patients of age 70 or older with previously untreated acute myeloid leukemia (AML): a North American Intergroup study (S0432). [Abstract] Blood 110 (11): A-440, 2007.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Harry Erba, MD, PhD, Protocol chair		Ph: 734-647-8921; 800-865-1125

Cancer and Leukemia Group B

Richard Larson, MD, Protocol chair		Ph: 773-702-6783; 888-824-0200

Eastern Cooperative Oncology Group

Martin Tallman, MD, Protocol chair		Ph: 312-695-0990

Related Information

Featured trial article

Registry Information
Official Title		Phase II Studies of Two Different Schedules and Two Different Doses of the Farnesyl Transferase Inhibitor R11577 (Tipifarnib, Zarnestra®, NSC-702818) For Previously Untreated Acute Myeloid Leukemia (AML) in Patients of Age 70 or Older
Trial Start Date		2004-09-15
Registered in ClinicalTrials.gov		NCT00093418
Date Submitted to PDQ		2004-08-13
Information Last Verified		2006-02-16
NCI Grant/Contract Number		CA32102

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