Arsenic Trioxide and Etanercept in Treating Patients With Myelodysplastic Syndromes

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Therapy of Advanced Stage Myelodysplastic Syndrome (MDS) With Arsenic Trioxide Given in Combination With Etanercept: A Phase I/II Study

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Intervention / Treatment
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* Biological: etanercept
* Drug: arsenic trioxide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: etanercept|nan|
|Drug: arsenic trioxide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic response in patients with intermediate-2 or high-risk myelodysplastic syndromes |  |  | 
| 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 on phenotypic, cytogenetic, and functional disease characteristics with in vivo treatment responses |  |  | 
| Parameters that are associated with a high probability of response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, myelodysplastic/myeloproliferative disease, unclassifiable, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia