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

NCT ID: NCT00104806

Last Updated: 2018-08-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30
• Study Completion Date: 2010-05-31

Brief Summary

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

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.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cholecalciferol

100 milligrams orally once a day for 28 days

Intervention Type: DIETARY_SUPPLEMENT

arsenic trioxide

0.3 milligram/kilogram weight intravenously for 5 days (loading) then 0.25/kg weight intravenously biweekly

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• 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

• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Istvan Molnar, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Locations

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

CCCWFU-29304

Identifier Type: -

Identifier Source: secondary_id

CCCWFU-BG04-452

Identifier Type: -

Identifier Source: secondary_id

CDR0000415574

Identifier Type: -

Identifier Source: org_study_id