RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by peripheral stem cell transplantation in treating patients who have myelofibrosis.

Condition	Treatment or Intervention	Phase
idiopathic myelofibrosis Polycythemia Vera Essential Thrombocythemia Agnogenic Myeloid Metaplasia	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: peripheral blood stem cell transplantation  Procedure: cytokine therapy  Drug: bone marrow ablation with stem cell support  Drug: busulfan  Drug: cytarabine  Drug: filgrastim  Drug: idarubicin	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the ability of myeloablative chemotherapy followed by peripheral blood stem cell (PBSC) transplantation to restore effective marrow hematopoieses in patients with advanced idiopathic myelofibrosis or myelofibrosis secondary to other myeloproliferative disorders. II. Determine the ability of this regimen to palliate symptoms and prolong survival in these patients. III. Determine if there is evidence of clonal hematopoieses before PBSC mobilization, in the PBSC product, and after transplantation in these patients. IV. Correlate the properties of the peripheral blood before mobilization and the PBSC product with engraftment in these patients. V. Correlate the markers of angiogenesis with clinical parameters in these patients.

PROTOCOL OUTLINE: Patients with evidence of leukemic progression receive cytoreduction therapy consisting of idarubicin IV on days 1-3 and cytarabine IV continuously over days 1-7 followed by filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover and leukapheresis is completed. Patients undergo leukapheresis beginning when blood counts recover and continuing until the target number of cells are collected. Patients with no evidence of leukemic progression receive filgrastim SC daily until leukapheresis is completed. Patients undergo leukapheresis beginning on day 4 and continuing until the target number of cells are collected. Patients receive myeloablative therapy consisting of oral busulfan every six hours on days -5 to -2. Patients with leukemic progression begin myeloablative therapy at least 28 days after completion of chemotherapy. Patients receive autologous peripheral blood stem cells IV on day 0. Patients are followed at 1 month, 3 months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 50 patients will be accrued for this study within 3 years.

Ages Eligible for Study:  up to  75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of idiopathic myelofibrosis or other myeloproliferative disorder with myelofibrosis
• Evidence of advanced disease or hematologic abnormalities due to severe fibrosis such as 1 or more of the following poor prognostic factors: Hemoglobin less than 10 g/dL; Platelet count less than 100,000/mm3; WBC less than 4,000/mm3; Symptomatic splenomegaly; Constitutional symptoms inadequately controlled with low dose chemotherapy; Abnormal karyotype
• Patients without evidence of advanced disease undergo PBSC harvest and transplantation is delayed until there is evidence of disease progression
• Leukemia progression (greater than 15% peripheral blood blasts) allowed if the history of a chronic myeloproliferative disorder of at least 6 months duration is well documented
• Ineligible for or refusal of allogeneic transplantation
• No other cause of myelofibrosis other than myeloproliferative disorders, such as the following: Metastatic carcinoma; Lymphoma; Hairy cell leukemia; Myelodysplastic syndrome; De novo acute leukemia; Collagen vascular disorders; Granulomatous infections

--Prior/Concurrent Therapy--

• See Disease Characteristics
• At least 7 days since prior hydroxyurea

--Patient Characteristics--

• Age: 75 and under
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics; WBC no greater than 30,000/mm3 (may be reduced to less than 30,000/mm3 using hydroxyurea or induction chemotherapy)
• Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN)*; Transaminases no greater than 2 times ULN*; * Unless due to extramedullary hematopoiesis in the liver
• Renal: Creatinine no greater than 2 times normal OR Creatinine clearance at least 50%
• Cardiovascular: No prior or active congestive heart failure*; LVEF at least 50%*; *If receiving study cytoreductive therapy
• Pulmonary: Total lung capacity at least 50% predicted OR Corrected DLCO at least 50% predicted
• Other: No active infection; No poorly controlled seizure disorders; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective barrier contraception; HIV negative

Alaska
      Katmai Oncology Group, Anchorage,  Alaska,  99508-4627,  United States
Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Illinois
      University of Illinois College of Medicine, Chicago,  Illinois,  60612,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Missouri
      Washington University Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
New York
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States
France
      Hopital Saint-Louis, Paris,  75475,  France
United Kingdom, England
      Addenbrooke's NHS Trust, Cambridge,  England,  CB2 2QQ,  United Kingdom

Study chairs or principal investigators

Jeanne E. Anderson,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000068240; FHCRC-1006.00; NCI-G00-1866; MCC-12245; MCC-IRB-5698
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  October 4, 2000
ClinicalTrials.gov Identifier:  NCT00006367
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08