Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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

PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating patients who have myelofibrosis with myeloid metaplasia.

Further Study Information

OBJECTIVES:

• Determine the response rate in patients with myelofibrosis with myeloid metaplasia treated with tipifarnib.

• Determine the toxicity of this drug in these patients.

• Determine the effect of this drug on disease-associated anemia, palpable splenomegaly, and hypercatabolic symptoms in these patients.

• Determine the effect of this drug on the pathologic increase in circulating myeloid progenitors from baseline to after the first course in these patients.

• Correlate response/relapse in these patients with in vitro myeloid colony sensitivity to this drug.

• Determine the effect of this drug on bone marrow histologic features (osteosclerosis, reticulin fibrosis, and angiogenesis) in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 15 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed myelofibrosis with myeloid metaplasia

• Agnogenic myeloid metaplasia

• Post-polycythemic myeloid metaplasia

• Post-thrombocythemic myeloid metaplasia

• Bone marrow must show reticulin fibrosis and peripheral blood smear must show leukoerythroblastosis and dacrocytosis

• Bone marrow must not show evidence of other conditions associated with myelofibrosis, including the following:

• Metastatic carcinoma

• Lymphoma

• Myelodysplasia

• Hairy cell leukemia

• Mast cell disease

• Acute leukemia (including M7 type)

• Acute myelofibrosis

• Absence of chromosomal translocation t(9:22) by bone marrow chromosome analysis or peripheral blood or bone marrow fluorescent in situ hybridization (FISH)

• At least 1 of the following must be present:

• Anemia evidenced by hemoglobin less than 10 g/dL

• Palpable hepatosplenomegaly

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

• Absolute neutrophil count at least 750/mm^3

• Platelet count at least 100,000/mm^3

Hepatic

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

• AST no greater than 2.5 times ULN

• Alkaline phosphatase no greater than 3 times ULN (unless secondary to disease)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other concurrent uncontrolled illness or comorbid condition that would preclude study participation

• No ongoing or active infection

• No psychiatric illness or social situation that would preclude study participation

• No known quinolone sensitivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent epoetin alfa

• No concurrent prophylactic colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])

• No concurrent thalidomide

Chemotherapy

• More than 2 weeks since prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 2 weeks since prior myelosuppressive agents

• No other concurrent therapy directed at the disease

Trial Contact Information

Trial Lead Organizations/Sponsors

Mayo Clinic Cancer Center

Ruben A. Mesa

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00047190
Information obtained from ClinicalTrials.gov on December 14, 2011

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