Ph II Study of Azacitidine in Myelofibrosis

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if azacitidine can help to control MF. The safety of azacitidine in patients with Myelofibrosis (MF) will also be studied.

Detailed Description
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Azacitidine is a drug that is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the bad genes, the tumor-fighting genes may be able to work better. If you are found to be eligible to take part in this study, you will be able to begin treatment with azacitidine. You will receive azacitidine as an injection under the skin once a day for 7 days in a row. This will be repeated every 4 weeks (4 weeks equals 1 cycle). The first cycle of azacitidine will be given at M. D. Anderson, in an outpatient setting. Later cycles of treatment courses may be given at M. D. Anderson or by a cancer doctor in your community. You may receive up to 12 cycles of treatment if you are responding well to treatment. You will be taken off study if your disease gets worse or intolerable side effects occur. Once you go off study, you will receive follow-up as is standard of care for your disease. This is an investigational study. Azacitidine is FDA approved for the treatment of myelodysplastic syndrome. Its use in this study is experimental. A total of up to 34 patients will take part in this study. All will be enrolled at M. D. Anderson.

Official Title
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Phase II Study of Azacitidine in Myelofibrosis

Conditions
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Myelofibrosis

Intervention / Treatment
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* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MF requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to Lille scoring system (adverse prognostic factors are: Hemoglobin (Hb) < 10 g/dl, White Blood Cell (WBC) < 4 or > 30 x 10*9/L; risk group: 0 = low, 1 = intermediate, 2 = high). Performance 0-2 Eastern Cooperative Oncology Group (ECOG). Signed informed consent. Patients must have been off chemotherapy for 2 weeks prior to entering this study and have recovered from the toxic effects (grade 0-1) of that therapy. Patients are allowed to be on anagrelide and hydroxyurea to control high platelet and WBC counts for their safety. Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory Upper Limit of of Normal(ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels </= 2 x ULN. Serum creatinine levels </= 1.5 x ULN; unless related to the MF, as judged by treating physicians. Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment and should be advised to avoid becoming pregnant. Men must be advised to not father a child while receiving treatment with azacitidine. Both women of childbearing potential and men must practice effective methods of contraception (those generally accepted as standard of care measures). Age >/= 18. Exclusion Criteria: Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements. Known or suspected hypersensitivity to azacitidine or mannitol.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azacitidine<br>75 mg/m^2 Subcutaneous Daily for 7 days every 4 weeks | Drug: Azacitidine<br>* 75 mg/m^2 subcutaneous daily for 7 days (every 4 week cycle)<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Clinical Response | Objective Clinical Response includes Participants with Complete Response, Partial Response or Hematologic Improvement and No Response. Bone marrow aspiration and biopsy with cytogenetics every 2 to 4 courses. | Every 2 courses of 4 week therapy = each 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelofibrosis, MF, Leukemia, Azacitidine, Vidaza