Tipifarnib in Treating Patients With Myelodysplastic Syndromes

Chronic Myelomonocytic Leukemia Clinical Trial

Official title:

Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005845
• Other study ID #: NCI-2009-01158
• Secondary ID: NCI-2009-01158CD
• Status: Completed
• Phase: Phase 1
• First received: June 2, 2000
• Last updated: December 13, 2013
• Start date: June 2002

Study information

• Verified date: December 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Anemia, Refractory, with Excess of Blasts
• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndromes
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndromes
• Preleukemia
• 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
• Syndrome

Intervention

Drug:
• tipifarnib
Given PO

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria	The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.	Up to 8.5 years	Yes
Primary	Response rate	Will be reported overall and by dose level.	Up to 8.5 years	No
Secondary	FTase inhibition	Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).	Up to 8.5 years	No
Secondary	Accumulation of unfarnesylated lamin B1	Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).	Up to 8.5 years	No
Secondary	Accumulation of RAS proteins	Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).	Up to 8.5 years	No