Azacitidine in Treating Patients With Myelofibrosis

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well azacitidine works in treating patients with myelofibrosis.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of azacitidine in patients with myelofibrosis (MF) with myeloid metaplasia. Evaluate the safety of azacitidine in these patients. Secondary Evaluate pertinent biologic characteristics of MF before and during therapy with azacitidine. Assess the effects of study treatment on constitutional symptoms in these patients. Estimate time to event distributions for overall survival and progression. OUTLINE: Patients receive azacitidine subcutaneously once daily on days 1-5. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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Phase II Study of Azacitidine in Myelofibrosis

Conditions
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Chronic Myeloproliferative Disorders, Secondary Myelofibrosis

Intervention / Treatment
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* Drug: azacitidine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed myelofibrosis with myeloid metaplasia (MMM), including any of the following subtypes: Agnogenic myeloid metaplasia Post-polycythemic myeloid metaplasia Post-thrombocythemic myeloid metaplasia Evaluable and symptomatic disease, defined as 1 of the following: Anemia (hemoglobin < 10 g/dL or erythrocyte transfusion-dependent, requiring 1 transfusion ≤ 8 weeks) Treatment required* for symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) NOTE: *Subjective but painful enough to mandate intervention Absence of t(9;22) by fluorescent in situ hybridization (FISH) or standard cytogenetics (by peripheral blood or marrow) - Previous demonstration of a lack of this translocation (at any point) is sufficient No advanced malignant hepatic tumors PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 50,000/mm³ Creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 2.0 mg/dL OR direct bilirubin ≤ 2.0 mg/dL if total bilirubin elevated (unless attributed to underlying disease) AST and ALT ≤ 2 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No baseline peripheral or autonomic neuropathy ≥ grade 2 No condition, including the presence of laboratory abnormalities, that would preclude study compliance No hypersensitivity to mannitol or azacitidine Not incarcerated in a municipality (i.e., county, state, or federal prison) PRIOR CONCURRENT THERAPY: At least 14 days since prior chemotherapy, including interferon alfa, anagrelide, or other myelosuppressive agents At least 14 days since prior systemic corticosteroids At least 14 days since prior investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: azacitidine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients With Confirmed Response (Complete Remission or Partial Remission on 2 Consecutive Evaluation at Least 4 Weeks Apart) During the First 4 Months of Treatment | Response Definitions: Completion Remission (CR):complete resolution of disease-related symptoms, ultrasound-documented resolution of hepastosplenomegaly, normalization of the peripheral blood count, white cell differential, and smear, normalization of bone marrow histology including disappearance of fibrosis and osteosclerosis. Residual cytogenetic abnormalities are allowed. Partial Remission (PR): a major response in any baseline applicable criteria (except constitutional symptoms) without progression in any other category. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from registration to death due to any cause or time from registration to 3 years after registration if patient is still alive. | From date of registration until death or 3 years after registration if patient is still alive | 
| Time to Progression | Time to progression was defined as the time from registration to progression of disease. Those who die without documentation of disease progression will be considered to have had disease progression at the time of their death unless documented evidence clearly indicates no progression has occured. | up to 3 years | 
| Number of Participants With Treatment Related Adverse Events | Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE. Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE | Every 4 weeks during treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary myelofibrosis, polycythemia vera, essential thrombocythemia, secondary myelofibrosis