Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

NCT ID: NCT00027872

Last Updated: 2013-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2009-01-31

Brief Summary

Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating older patients who have previously untreated acute myeloid leukemia

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the complete response rate of R115777 (tipifarnib) in previously untreated acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >= 65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule.

SECONDARY OBJECTIVES:

I. To determine progression-free and overall survival in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.

II. To determine the duration of response in patients with previously untreated AML treated with R115777, using a chronic dosing schedule.

III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K) in leukemic cells.

IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2.

V. To determine the toxicities of R115777 when given in a chronic dosing schedule.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.

Conditions

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); 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 Del(5q); 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); Cellular Diagnosis, Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (tipifarnib)

Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.

Group Type: EXPERIMENTAL

tipifarnib

Intervention Type: DRUG

Given orally

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

tipifarnib

Given orally

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

R115777; Zarnestra

Eligibility Criteria

Inclusion Criteria

• Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts)
• ECOG performance status 0 or 1
• Patients must be able to give informed consent
• SGOT and SGPT =< 2.5 x normal limits (grade 1)
• Serum creatinine =< 1.5 x normal limits (grade 1)
• AML (any of the following):

• Newly diagnosed AML in adults >= 75 years
• Newly diagnosed AML arising from MDS in adults >= 65 years
• Hyperleukocytosis with >= 30,000 leukemic blasts/uL

Exclusion Criteria

• Acute promyelocytic (FAB M3) subtype
• Previously treated with chemotherapy for leukemia (except for hydroxyurea)
• Disseminated intravascular coagulation (laboratory or clinical)
• Active central nervous system leukemia
• Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments
• Intrinsic impaired organ function (as stated above)
• Symptomatic neuropathy (grade 2 or worse)
• Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole
• Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Karp

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

UMGCC 0116

Identifier Type: -

Identifier Source: secondary_id

U01CA069854

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02980

Identifier Type: -

Identifier Source: org_study_id