A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

NCT ID: NCT00045396

Last Updated: 2013-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30

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 patients who have acute myeloid leukemia or myelodysplastic syndrome in first complete remission

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the duration of disease-free survival (DFS) and overall survival (OS) when ZARNESTRA is administered after intensive induction and consolidation chemotherapy to adults with poor risk acute myelogenous leukemia (AML) or high-risk myelodysplasia (MDS) in first complete remission (CR).

SECONDARY OBJECTIVES:

I. To determine the tolerability and toxicities of ZARNESTRA when administered in a chronic dosing schedule over a 48 week period to adults in first CR following intensive cytotoxic chemotherapies.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 14-44 patients will be accrued for this study within 11-15 months.

Conditions

Adult Acute Myeloid Leukemia in Remission; 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(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); de Novo Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

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 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

tipifarnib

Intervention Type: DRUG

Given orally

Interventions

tipifarnib

Given orally

Intervention Type: DRUG

Other Intervention Names

R115777; Zarnestra

Eligibility Criteria

Inclusion Criteria

• Pathological Confirmation of the Diagnosis of AML, MDS
• PMNs >= 1,000/ul
• Platelets >= 30,000/ul
• Hematocrit >= 27% and/or Hemoglobin >= 9 gm/dl unsupported
• ECOG Performance Status 0-2
• Patients must be able to give informed consent
• Female patients of childbearing age must have negative pregnancy test
• AST, ALT and Alkaline Phosphatase =<2.5 x normal
• Bilirubin =< 1.5 x normal
• Serum Creatinine =< 2.0 mg/dl or Creatinine Clearance >= 40 ml/min
• Left Ventricular Ejection Fraction >= 25%
• Patients with poor-risk AML or high-risk MDS who have completed both induction and consolidation chemotherapy; poor risk AML is defined by one or more of the following characteristics:

• Antecedent Hematologic Disorder
• AML Arising from MDS
• Therapy-related AML
• Age >= 60 (in absence of favorable cytogenetics)
• Adverse Cytogenetics (i.e., -5/5q, -7/7q, +8, 20q-, 11q23 abnormalities, complex karyotype; other abnormalities may be considered at discression of study chair)
• Hyperleukocytosis at diagnosis (Blasts >= 30,000/mm^3 at diagnosis in absence of favorable cytogenetics)

High Risk MDS is defined by one or more of the following characteristics:

• RAEB and RAEB-t, with IPSS Score >= 1.5 (adverse cytogenetics, > 10% marrow blasts, cytopenias in at least 2 lineages): See Appendix E (Greenberg, et al. Blood 89:2079-2088,1997)36
• CMML with > 5% marrow blasts
• Therapy-related MDS

Exclusion Criteria

• Any previous treatment with ZARNESTRA
• Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial)
• Acute promyelocytic (FAB M3) subtype
• Presence of (8;21) translocation or inversion 16 genotype as sole abnormality
• Eligible for curative allogeneic stem cell transplantation
• Known allergy to imidazole drugs (e.g., ketoconazole, miconazole)
• Presence of Residual AML (> 5% marrow blasts) or MDS, as Determined by Morphology, Flow Cytometry, and/or Cytogenetics
• Active, Uncontrolled Infection
• Disseminated Intravascular Coagulation
• Active CNS Leukemia
• Concomitant Chemotherapy, Radiation Therapy or Immunotherapy
• Women who are pregnant or lactating will not be eligible for this trial, as the investigational agent may be harmful to the developing fetus or nursing infant

• Minimum Eligible Age: 18 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

J0252

Identifier Type: -

Identifier Source: secondary_id

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA069854

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-03158

Identifier Type: -

Identifier Source: org_study_id