Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Myelofibrosis/Myeloproliferative Disorder
Condition: Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): ascorbic acid; arsenic trioxide; dexamethasone; thalidomide
Intervention type(s): Dietary Supplement; Drug; Drug; Drug
Intervention description(s): 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.
Other intervention name(s): vitamin C; Trisenox®; ATO; Thalomid®
Intervention MeSH terms: Ascorbic Acid; Thalidomide; Dexamethasone; Arsenic Trioxide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chronic idiopathic myelofibrosis; chronic myelomonocytic leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes