Tipifarnib in Treating Patients With Myelodysplastic Syndromes

NCT00005845 | Completed Phase 1

• 5 other identifiers: NCI-2009-01158CDR0000067862DM01-5825625U01CA062461
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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

• Response rate

  Will be reported overall and by dose level.

  Up to 8.5 years

Secondary Outcomes (3)

• FTase inhibition

  Up to 8.5 years

• Accumulation of unfarnesylated lamin B1

  Up to 8.5 years

• Accumulation of RAS proteins

  Up to 8.5 years

Study Arms (1)

Treatment (tipifarnib)

EXPERIMENTAL

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.

Drug: tipifarnib; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

tipifarnib DRUG

Given PO

Also known as: R115777, Zarnestra

Treatment (tipifarnib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (tipifarnib)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (tipifarnib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia; Myelodysplastic Syndromes

Study Officials

• Razelle Kurzrock

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2000
• First Posted: August 29, 2003
• Study Start: June 1, 2002
• Primary Completion: September 1, 2009
• Last Updated: December 16, 2013

Record last verified: 2013-12

Locations

US (1)