Arsenic Trioxide and Etanercept in Treating Patients With Myelodysplastic Syndromes
Arsenic Trioxide and Etanercept in Treating Patients With Myelodysplastic Syndromes
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to
 stop cancer cells from dividing so they stop growing or die. Biological therapies such as
 etanercept may interfere with the growth of the cancer cells. Combining chemotherapy with
 biological therapy may kill more cancer cells.

 PURPOSE: This phase I/II trial is studying the side effects of giving arsenic trioxide
 together with etanercept and to see how well it works 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