Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

Study Overview
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Brief Summary
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This phase I/II trial studies how well giving azacitidine together with etanercept works in treating patients with myelodysplastic syndromes (MDS). Drugs used in chemotherapy, such as azacitidine, works in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as etanercept, may protect normal cells from the side effects of chemotherapy

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the frequency of hematologic responses in patients with MDS to 5-aza (azacitidine) plus etanercept. II. Determine the efficacy of 5-aza combined with etanercept in patients with low or intermediate (int)-1 risk who fail to respond to anti-thymocyte globulin (ATG) plus etanercept and for the purpose of this trial are considered as having progressive or more advanced disease. III. Correlate results of ex vivo/in vitro studies on phenotypic, cytogenetic and functional disease characteristics with in vivo treatment responses, to identify parameters that are associated with a high probability of response. OUTLINE: Patients receive etanercept subcutaneously (SC) twice weekly during weeks 1 and 2 and azacitidine SC or intravenously (IV) over 10-40 minutes on days 1-7. Treatment repeats every 28 days for at least 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Official Title
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Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.

Conditions
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de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: azacitidine
* Biological: etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Int-2 or high risk MDS patients Patients with low-risk or int-1 risk MDS by International Prognostic Scoring System (IPSS) criteria with: Single or multilineage cytopenia (absolute neutrophil count [ANC] < 1500/μL, hemoglobin [Hgb],10g/dL, or platelet count < 100,000/μL); or Transfusion requirement of at least 2 units of packed red blood cells over an 8 week period Serum creatinine =< 1.5x ULN (upper limit of normal) Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2x ULN Performance status =< 2 (Eastern Cooperative Oncology Group [ECOG] scale, 0-5) Exclusion Criteria: Patients who have previously received hematopoietic stem cell transplants, specifically for MDS Patients with a diagnosis of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria (i.e >= 20% blasts) at time of enrollment Women of child bearing potential who are currently pregnant, lactating or who are not willing to use contraception during the entire duration of the study Men who are unwilling to use contraception while receiving 5-aza Patients with severe disease other than MDS which is expected to prevent compliance with the present protocol Patients with severe infections (pneumonia, septicemia, etc) within the 2 weeks prior to the anticipated start of protocol treatment Patients who are currently receiving or within the preceding 2 weeks have received cytotoxic therapy, hemopoietic growth factors, immunomodulatory therapy, or other experimental therapy for the treatment of MDS Current evidence of uncontrolled cardiac arrhythmia or congestive heart failure Platelet count =< 10,000/mcl Absolute neutrophil count =< 250/mcl Prior treatment with 5-aza 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy, chemoprotection)<br>Patients receive etanercept SC twice weekly during weeks 1 and 2 and azacitidine SC or IV over 10-40 minutes on days 1-7. Treatment repeats every 28 days for at least 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. | Drug: azacitidine<br>* Given SC or IV<br>* Other names: Vidaza;Biological: etanercept<br>* Given SC<br>* Other names: Tumor Necrosis Factor Receptor IgG Chimera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Hematologic Responses, as Defined by International Working Group (IWG) Criteria | Count of participants with a hematologic improvement (erythroid, platelet, or neutrophil response), assessed at 3 months. | Up to 2 years |