Arsenic Trioxide and Cholecalciferol (Vitamin D) in Treating Patients With Myelodysplastic Syndromes

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Cholecalciferol (vitamin D) may help cancer cells become normal cells. Giving arsenic trioxide together with cholecalciferol (vitamin D) may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with cholecalciferol (vitamin D) works in treating patients with myelodysplastic syndromes.

Detailed Description
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OBJECTIVES: Primary Determine the complete response rate and the rate of hematological improvement in patients with myelodysplastic syndromes treated with arsenic trioxide and cholecalciferol (vitamin D). Secondary Determine the safety of this regimen in these patients. Determine the time to progression to acute myeloid leukemia, defined as blast ≥ 20%, in patients treated with this regimen. Determine overall survival and progression-free survival of patients treated with this regimen. Determine the effect of this regimen on bone marrow and peripheral blood mononuclear cell apoptosis and p21 protein expression in these patients. OUTLINE: This is an open-label, nonrandomized study. Patients receive oral cholecalciferol (vitamin D)* once daily on days 1-28. Patients also receive arsenic trioxide IV over 1-4 hours on days 1-5 (week 1) and then twice weekly for 3 weeks (weeks 2-4) for course 1 and twice weekly for 4 weeks for all subsequent courses. Courses repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. NOTE: * Patients who do not achieve a complete hematologic response receive escalating doses of cholecalciferol (vitamin D) at 3, 6, and 9 months during therapy in the absence of disease progression and unacceptable toxicity. At the completion of study treatment, patients are followed for survival. PROJECTED ACCRUAL: A total of 25-60 patients will be accrued for this study.

Official Title
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Phase II Trial of Arsenic Trioxide and Dose-Escalated Cholecalciferol in Myelodysplastic Syndrome

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Dietary Supplement: cholecalciferol
* Drug: arsenic trioxide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of myelodysplastic syndromes (MDS) Bone marrow aspirate and biopsy with karyotyping performed within the past 12 weeks PATIENT CHARACTERISTICS: Age Any age Performance status ECOG 0-2 Life expectancy More than 6 months Hematopoietic Ferritin ≥ 50 ng/mL Folate (serum and/or red blood cell) normal Hepatic Not specified Renal Creatinine < 2.0 mg/dL No history of hypercalcemia Cardiovascular Absolute QT interval ≤ 460 msec by EKG with normal potassium and magnesium levels Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 weeks after study participation Serum vitamin B_12 normal PRIOR CONCURRENT THERAPY: Biologic therapy Prior biologic therapy allowed More than 28 days since prior hematopoietic growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa) for MDS No concurrent hematopoietic growth factors (e.g., G-CSF, GM-CSF, or epoetin alfa) No concurrent interleukin-11 Chemotherapy Prior chemotherapy allowed Endocrine therapy Not specified Radiotherapy Prior radiotherapy allowed Surgery Not specified Other More than 28 days since prior therapy for MDS except supportive therapy No concurrent cholecalciferol (vitamin D) analog, including topical therapy No concurrent vitamins or supplements containing cholecalciferol (vitamin D) No other concurrent therapy for MDS

Ages Eligible for Study
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Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: cholecalciferol|100 milligrams orally once a day for 28 days|
|Drug: arsenic trioxide|0.3 milligram/kilogram weight intravenously for 5 days (loading) then 0.25/kg weight intravenously biweekly|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate |  | 6 months | 
| toxicity assessment after therapy |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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de novo myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, refractory anemia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, chronic myelomonocytic leukemia, childhood myelodysplastic syndromes