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

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.

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