RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of cancer cells. The cancer is said to be resistant to chemotherapy. Giving ascorbic acid may reduce drug resistance and allow the cancer cells to be killed. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide works in treating patients with chronic idiopathic myelofibrosis or myelodysplastic or myeloproliferative disorders.
OBJECTIVES: Primary * Evaluate the efficacy (in terms of response rate) of arsenic trioxide, ascorbic acid, dexamethasone, and thalidomide in patients with chronic idiopathic myelofibrosis or myelodysplastic/myeloproliferative disorders. Secondary * Determine the rate of disease progression or progression to acute leukemia in patients treated with this regimen. * Assess improvement in bone marrow pathology (including degree of fibrosis, percentage of blasts, and resolution of cytogenetic abnormalities) in patients treated with this regimen. * Determine time to response in patients treated with this regimen. * Determine the reduction of spleen size in patients treated with this regimen. * Measure clinical responses and quality of life in subgroups treated with this regimen. * Determine the safety of this regimen in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive arsenic trioxide IV over 1-2 hours for 5 days and oral ascorbic acid once daily for 5 days during week 1. Patients then receive arsenic trioxide and ascorbic acid twice a week in weeks 2-12. Patients also receive oral dexamethasone once daily for 5 days in weeks 1, 5, 9, and 12 and oral thalidomide once or twice daily in weeks 1-12. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and after every course. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
The dose of ascorbic acid will be 1000 mg PO 2-3 hours prior to ATO infusion. The treatment will follow the same schedule as arsenic trioxide.
Treatment consists of a loading period of five 0.25 mg/kg ATO doses in the first week, followed by maintenance dosing with 0.25 mg/kg ATO twice weekly for 11 weeks. Loading is usually done Monday through Friday of the first treatment week. Maintenance should be started either 72 or 96 hours after the last loading dose. Thereafter, dosing is twice weekly, following an alternating pattern of 72 and 96 hours. For example, maintenance dosing may be done on Mondays and Thursdays, Tuesdays and Fridays, etc. The same pattern should be followed for the entire maintenance dosing period.
Dexamethasone will be given at a dose of 4mg PO daily for five days every four weeks (i.e., days 1-5, 29-33, 57-61, 84-88, etc.).
The dose of thalidomide will be 50 mg PO daily starting day 1. The dose will be increased to 100mg PO daily after two weeks if tolerated and only if patients experience \< grade 1 thalidomide-attributed toxicity using CTC criteria.
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Response rate at 6 months
Patients with any improvement in disease status (hematologic improvement or partial remission for patients with higher risk disease) may continue on study until a major response or complete remission occurs. Study visits will occur weekly for the first four weeks, then every four weeks, for each cycle. Laboratory monitoring to assess hematological parameters will occur weekly for the first four weeks, then every four weeks, for each cycle.
Time frame: at 6months of therapy and followed for at least 4 weeks after
Bone marrow response at 6 months
Bone marrow aspirate / biopsy for morphology and blast count, iron stain and cytogenetics.
Time frame: at 6 months
Spleen size at 12 weeks
Ultrasound of the spleen
Time frame: at 12 weeks
Quality of life
Patients will complete the FACT-An questionnaire every 12 weeks.
Time frame: every 12 weeks
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