Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Tipifarnib in Treating Patients With Myelofibrosis and Myeloid Metaplasia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	MAYO-MC0184 NCI-5576, 5576, NCT00047190

Objectives

1. Determine the response rate in patients with myelofibrosis with myeloid metaplasia treated with tipifarnib.
2. Determine the toxicity of this drug in these patients.
3. Determine the effect of this drug on disease-associated anemia, palpable splenomegaly, and hypercatabolic symptoms in these patients.
4. Determine the effect of this drug on the pathologic increase in circulating myeloid progenitors from baseline to after the first course in these patients.
5. Correlate response/relapse in these patients with in vitro myeloid colony sensitivity to this drug.
6. Determine the effect of this drug on bone marrow histologic features (osteosclerosis, reticulin fibrosis, and angiogenesis) in these patients.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

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.

Mesa RA, Camoriano JK, Geyer SM, et al.: A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Leukemia 21 (9): 1964-70, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Ruben Mesa, MD, Protocol chair		Ph: 507-284-2511

Registry Information
Official Title		A Phase II Trial of R115777 in Myelofibrosis with Myeloid Metaplasia (MMM)
Trial Start Date		2002-08-16
Registered in ClinicalTrials.gov		NCT00047190
Date Submitted to PDQ		2002-08-15
Information Last Verified		2004-04-13
NCI Grant/Contract Number		CM17104, CA15083

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