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
- Evaluate the efficacy (in terms of response rate) of arsenic trioxide, ascorbic acid,
dexamethasone, and thalidomide in patients with chronic idiopathic myelofibrosis or
- 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
- 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
at 6months of therapy and followed for at least 4 weeks after
Mikkael A. Sekeres, MD, MS
The Cleveland Clinic
United States: Food and Drug Administration
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|