Arsenic Trioxide and Etanercept in Treating Patients With Myelodysplastic Syndromes

OBJECTIVES:

• Determine the frequency of hematologic response in patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS) treated with arsenic trioxide and etanercept.
• Determine the efficacy of this regimen in patients with intermediate-1 or low-risk MDS that was refractory to anti-thymocyte globulin and etanercept on protocol FHCRC-1872.
• Correlate results of ex vivo and in vitro studies of phenotypic, cytogenetic, and functional disease characteristics with in vivo treatment response in patients treated with this regimen.
• Determine parameters that are associated with a high probability of disease response in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 of week 1 and then twice weekly on weeks 2-12 during course 1 (twice weekly on weeks 1-12 during course 2). Patients also receive etanercept subcutaneously twice weekly during weeks 1, 2, 5, 6, 9, and 10. Treatment repeats every 12 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 15-32 patients will be accrued for this study within 8-18 months.

DISEASE CHARACTERISTICS:

• Diagnosis of myelodysplastic syndromes (MDS) meeting 1 of the following criteria:

• Intermediate-2 or high-risk disease
• Intermediate-1 or low-risk disease that was refractory to anti-thymocyte globulin and etanercept on protocol FHCRC-1872
• Not eligible for stem cell transplantation for any of the following reasons:

• Suitable bone marrow donor is not available
• Ineligible for a transplantation protocol
• Not willing to undergo transplantation

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 500/mm^3

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No evidence of cardiac arrhythmia
• No evidence of congestive heart failure
• QTc interval ≤ 460 msec

Pulmonary

• No pneumonia

Other

• Potassium > 4.0 mEq/L (supplemental electrolytes allowed)
• Magnesium > 1.8 mg/dL (supplemental electrolytes allowed)
• No history of anaphylactic reaction to arsenic trioxide
• No active severe infection (e.g., septicemia) within the past 2 weeks
• No other severe disease that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior hematopoietic stem cell transplantation
• More than 4 weeks since prior hematopoietic growth factors for MDS
• More than 4 weeks since prior immunomodulatory therapy for MDS
• No concurrent hematopoietic growth factors for MDS
• No other concurrent immunomodulatory therapy for MDS

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 4 weeks since prior cytotoxic therapy for MDS
• More than 4 weeks since prior experimental therapy for MDS
• No other concurrent cytotoxic therapy for MDS
• No other concurrent experimental therapy for MDS