Tipifarnib in Treating Patients With Myelofibrosis and Myeloid Metaplasia - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00047190

Purpose

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.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders	Drug: tipifarnib	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Trial of R115777 in Myelofibrosis With Myeloid Metaplasia (MMM)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Spleen Diseases

Drug Information available for: R 115777 Tipifarnib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

August 2002

Detailed Description:

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047190

Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259
United States, District of Columbia
Howard University College of Medicine
Washington, District of Columbia, United States, 20059
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Ruben A. Mesa, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Mesa RA, Camoriano JK, Geyer SM, Wu W, Kaufmann SH, Rivera CE, Erlichman C, Wright J, Pardanani A, Lasho T, Finke C, Li CY, Tefferi A. A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Leukemia. 2007 Jun 21; [Epub ahead of print]

Study ID Numbers:	CDR0000257568, MAYO-MC0184, NCI-5576
Study First Received:	October 3, 2002
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00047190 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

chronic idiopathic myelofibrosis
polycythemia vera
essential thrombocythemia

Additional relevant MeSH terms:

Myelofibrosis
Hematologic Diseases
Antineoplastic Agents
Myeloproliferative Disorders
Pharmacologic Actions
Myeloid Metaplasia
Lymphatic Diseases

Pathologic Processes
Metaplasia
Therapeutic Uses
Bone Marrow Diseases
Splenic Diseases
Tipifarnib

ClinicalTrials.gov processed this record on November 25, 2009