Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Myelofibrosis/Myeloproliferative Disorder
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.
|Chronic Myeloproliferative Disorders Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases||Dietary Supplement: ascorbic acid Drug: arsenic trioxide Drug: dexamethasone Drug: thalidomide||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Combination Therapy With Thalidomide, Arsenic Trioxide, Dexamethasone, and Ascorbic Acid (TADA) in Patients With Chronic Idiopathic Myelofibrosis or Overlap Myelodysplastic/Myeloproliferative Disorders|
- Response rate at 6 months [ Time Frame: at 6months of therapy and followed for at least 4 weeks after ]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.
- Bone marrow response at 6 months [ Time Frame: at 6 months ]Bone marrow aspirate / biopsy for morphology and blast count, iron stain and cytogenetics.
- Spleen size at 12 weeks [ Time Frame: at 12 weeks ]Ultrasound of the spleen
- Quality of life [ Time Frame: every 12 weeks ]Patients will complete the FACT-An questionnaire every 12 weeks.
|Study Start Date:||October 2005|
|Study Completion Date:||October 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
Dietary Supplement: ascorbic acid
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00274820
|United States, Ohio|
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44195|
|Study Chair:||Mikkael A. Sekeres, MD, MS||The Cleveland Clinic|