Leukemia, Myelodysplastic/Myeloproliferative Diseases, Myelodysplastic Syndromes
Conditions
Keywords
de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, myelodysplastic/myeloproliferative disease, unclassifiable, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia
Brief summary
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
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.
Interventions
BIOLOGICALetanercept
DRUGarsenic trioxide
Sponsors
National Cancer Institute (NCI)
Fred Hutchinson Cancer Center
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | 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 | — |
Countries
United States
Outcome results
None listed