Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

Phase 1

Completed

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy, chemoprotection)	azacitidine	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.
Treatment (chemotherapy, chemoprotection)	etanercept	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.

Primary Outcome Measures

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

Secondary Outcome Measures