RATIONALE: Imatinib mesylate may stop the growth of myelofibrosis by blocking certain enzymes necessary for cell growth.

PURPOSE: Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have myelofibrosis.

Condition	Treatment or Intervention	Phase
Polycythemia Vera chronic idiopathic myelofibrosis Essential Thrombocythemia Chronic Myelomonocytic Leukemia	Drug: imatinib mesylate  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the complete and partial response rate in patients with myelofibrosis treated with imatinib mesylate.
• Determine the safety of this drug in these patients.
• Determine the effects of this drug on the bone marrow morphology, including effects on bone marrow fibrosis, osteosclerosis, and cellularity, in these patients.
• Assess the effects of this drug on surrogate biologic endpoints, including platelet-derived growth factor (PDGFR) expression by immunohistochemistry, PDGFR signaling, and circulating progenitor (CD34 positive) cells, in these patients.
• Determine the effects of this drug on bone marrow cytogenetics in patients with an abnormal karyotype.

OUTLINE: This is a multicenter study. Patients are stratified according to Dupriez risk score (low vs intermediate vs high).

Patients receive oral imatinib mesylate once or twice daily on days 1-28. Courses repeat every 28 days for 12 months in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study within 3-17.5 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• One of the following diagnoses:
• Histologically confirmed myeloid metaplasia with myelofibrosis (MMM)
• All subtypes eligible
• Chronic idiopathic myelofibrosis
• Agnogenic myeloid metaplasia
• Post-thrombocythemic or post-polycythemic myelofibrosis
• Must meet the standard Italian Diagnostic Criteria for MMM OR
• Histologically confirmed chronic myelomonocytic leukemia (CMMOL) with t(5;12)(q31;p12) or TEL-platelet-derived growth factor (PDGFR)-beta rearrangement
• Patients with CMMOL and the t(5;7)(q33;q11.2) or other chromosomal translocations resulting in activation of PDGFR are also eligible
• Must meet the standard World Health Organization Diagnostic Criteria for CMMOL
• Meets criteria for 1 of the following:
• Anemia (hemoglobin less than 11 g/dL)
• Splenomegaly by palpation and ultrasound
• Philadelphia chromosome or bcr-abl rearrangement negative

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST/ALT less than 2.5 times ULN (unless due to liver involvement with disease)

Renal:

• Creatinine less than 2 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 barrier contraception during and for up to 3 months after study participation
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to imatinib mesylate
• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situations that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior epoetin alfa or filgrastim (G-CSF)
• No concurrent biologic agents

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior androgenic steroids
• No concurrent androgenic steroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy, including splenic irradiation
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• At least 4 weeks since other prior therapy
• Any number of prior treatment regimens allowed
• No other concurrent investigational or commercial anticancer agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent therapeutic anticoagulation with warfarin
• Concurrent therapeutic anticoagulation with low-molecular weight heparin (e.g., enoxaparin) or unfractionated heparin allowed

Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153,  United States; Recruiting
      Central Illinois Hematology Oncology Center, Springfield,  Illinois,  62701,  United States; Recruiting
      Decatur Memorial Hospital Cancer Care Institute, Decatur,  Illinois,  62526,  United States; Recruiting
      Evanston Northwestern Health Care - Evanston Hospital, Evanston,  Illinois,  60201-1781,  United States; Recruiting
      Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States; Recruiting
      La Grange Memorial Hospital, La Grange,  Illinois,  60525,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Michigan
      Oncology Care Associates, P.L.L.C., Saint Joseph,  Michigan,  49085,  United States; Recruiting

Study chairs or principal investigators

Olatoyosi M. Odenike, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000069381; UCCRC-11498A; NCI-5669; NCT00039416
Record last reviewed:  August 2002
Last Updated:  April 4, 2005
Record first received:  June 6, 2002
ClinicalTrials.gov Identifier:  NCT00039416
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08