Tipifarnib in Treating Patients With Myelodysplastic Syndromes

NCT ID: NCT00005845

Last Updated: 2013-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30

Brief Summary

This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the toxicity profile and antitumor activity of the farnesyltransferase (FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS) treated on a one week on/one week off schedule.

II. To determine the effect on R115777 on a one week on/one week off schedule on FTase activity, prenylation of RAS and other substrates and on downstream effects.

OUTLINE: This is a dose-escalation study.

Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Conditions

Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia

Study Design

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

Study Groups

Treatment (tipifarnib)

Patients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

tipifarnib

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

tipifarnib

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

R115777; Zarnestra; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically MDS (including French-American-British [FAB] types refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose of the study, all patients will be classified by World Health Organization (WHO) criteria

• By these criteria, FAB RA are split into:
• Pure dyserythropoietic refractory anemia (PRA)

• Refractory cytopenia with multilineage dysplasia (RCMD)
• FAB RARS is split into:

• Pure sideroblastic anemia (PSA)
• Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD)
• FAB RAEB is split into:

• RAEB I (< 10% BM blasts)
• RAEB II (10-20% BM blasts)
• Patients with CMMoL, and RAEBT by FAB classification will be included in the protocol
• Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria
• =< 2 prior therapies
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 12 weeks
• Bilirubin =< 1.5mg %
• Creatinine =< 1.5mg %
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for UCN01) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777 (such as imidazoles)
• Patients eligible for bone marrow transplant (=< 60 years old), with a compatible sibling, no contraindications for transplant
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with R115777.
• Growth factors other than filgrastim (G-CSF) are excluded; patients should be off excluded growth factors for 2 weeks

• 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

Razelle Kurzrock

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

NCI-2009-01158

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000067862

Identifier Type: -

Identifier Source: secondary_id

DM01-582

Identifier Type: OTHER

Identifier Source: secondary_id

5625

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA062461

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-01158

Identifier Type: -

Identifier Source: org_study_id