Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

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.

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