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: Phase I/II trial to study the effectiveness of combining arsenic trioxide with etanercept in treating patients who have myelodysplastic syndromes.

Condition	Treatment or Intervention	Phase
de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes myelodysplastic/myeloproliferative disease, unclassifiable atypical chronic myeloid leukemia Chronic Myelomonocytic Leukemia	Drug: arsenic trioxide  Drug: etanercept  Procedure: anti-cytokine therapy  Procedure: anti-tumor necrosis factor therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy	Phase I Phase II

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 and studies of phenotypic, cytogenetic, and functional disease characteristics with 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

Bart L. Scott, MD,  Principal Investigator,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000380742; FHCRC-1888.00
Record last reviewed:  September 2004
Record first received:  October 6, 2004
ClinicalTrials.gov Identifier:  NCT00093366
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-29