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

Wake Forest University (WFU)

Status and phase

Terminated

Phase 2

Conditions

Leukemia

Myelodysplastic Syndromes

Myelodysplastic/Myeloproliferative Neoplasms

Treatments

Drug: arsenic trioxide

Dietary Supplement: cholecalciferol

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00104806

CCCWFU-BG04-452

CDR0000415574

CCCWFU-29304

Details and patient eligibility

About

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.

Full description

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.

Enrollment

5 patients

Sex

All

Ages

Under 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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