Tipifarnib in Treating Patients With Myeloproliferative Disorders

Leukemia Clinical Trial

Official title:

Phase I/II Study of the Farnesyltransferase Inhibitor R115777 (NSC 702818) in Patients With Myeloproliferative Disorders

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00005846
• Other study ID #: CDR0000067864
• Secondary ID: SUMC-NCI-38NCI-3
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: June 2, 2000
• Last updated: June 4, 2011
• Start date: June 2000

Study information

• Verified date: July 2005
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: This phase I/II trial is studying the side effects of tipifarnib and to see how well it works in treating patents with myeloproliferative disorders.

Description:

OBJECTIVES:

• Determine the toxic effects of tipifarnib in adult patients with myeloproliferative disorders.

• Determine hematological responses, including changes in WBC count and erythroid responses, in this patient population treated with this drug.

• Determine the cytogenetic response in bone marrow of patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to prior substantive treatment (yes vs no).

Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 4 weeks for a maximum of 4 courses in the absence of unacceptable toxicity or disease progression. Patients with continued hematologic response after completion of the fourth course may receive additional courses at the discretion of the investigator.

PROJECTED ACCRUAL: A total of 25 patients (12-13 per stratum) will be accrued for this study within 25 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia (CML)

• Philadelphia chromosome (Ph) positive OR

• BCR-ABL positive by polymerase chain reaction

• Must meet 1 of the following 2 conditions:

• Chronic phase

• Persistent or progressive disease on maximum tolerated interferon or imatinib mesylate, as evidenced by increasing WBC count, peripheral blood myeloid immaturity, progressive anemia, and/or persistence or relapse of abnormal cytogenetics and/or molecular findings

• Interferon or imatinib mesylate intolerant

• Accelerated phase

• Persistent or progressive disease on imatinib mesylate

• Patients who have not received interferon or imatinib mesylate due to allergy or refusal are eligible OR

• Diagnosis of chronic myelomonocytic leukemia

• Proliferative type (WBC at least 12,000/mm3)

• Less than 5% blasts in peripheral blood and no more than 20% blasts in bone marrow OR

• Diagnosis of undifferentiated myeloproliferative disorder OR

• Diagnosis of atypical CML (Ph negative)

• No blast crisis phase of CML, atypical CML, or undifferentiated myeloproliferative disorders

• No more than 20% blasts in peripheral blood or bone marrow

• Diagnosed more than 3 months before study entry

PATIENT CHARACTERISTICS:

Age:

• 21 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 4 months

Hematopoietic:

• See Disease Characteristics

• No requirement for platelet transfusion

• No thrombocytopenia-related bleeding

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• AST/ALT no greater than 2 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Capable of swallowing capsules

• No other concurrent severe disease that would preclude study compliance

• No septicemia or other severe infection

• No iron deficiency

• If marrow aspirate not available, transferrin saturation at least 20% and ferritin greater than 50 ng/mL

• No other contributing causes of anemia (e.g., autoimmune or hereditary hemolytic disorders, gastrointestinal blood loss, B12 or folate deficiency, or hypothyroidism)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

• At least 4 weeks since prior interferon

• At least 4 weeks since prior hematopoietic growth factors

• No prior allogeneic bone marrow transplantation

Chemotherapy:

• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) except for hydroxyurea which may be used to manage elevated cell counts through the beginning of the second course of study therapy

Endocrine therapy:

• No concurrent androgens

• No concurrent corticosteroids (e.g., greater than 10 mg/day prednisone or equivalent steroid dosage) except as premedication for transfusions

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent standard or investigational cytotoxic agents

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders

Intervention

Drug:
• tipifarnib

Locations

Country	Name	City	State
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Gotlib J, Loh M, Vattikuti S, et al.: Phase I/II study of tipifarnib (ZARNESTRA, farnesyltransferase inhibitor [FTI] R115777) in patients with myeloproliferative disorders(MPDs): preliminary results. [Abstract] Blood 100 (Suppl 1): 798a, 2002.