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

This study has been terminated.
(sponsor discontinues support)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00104806
First received: March 3, 2005
Last updated: July 12, 2012
Last verified: July 2012
History of Changes

March 3, 2005
July 12, 2012
November 2004
January 2006   (final data collection date for primary outcome measure)
  • Complete response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • toxicity assessment after therapy [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Complete response rate
  • Time to progression
  • Rate of hematological improvement
Complete list of historical versions of study NCT00104806 on ClinicalTrials.gov Archive Site
 
  • Overall and progression-free survival
  • Change in bone marrow apoptosis and expression of p21 protein
 
 
 
Arsenic Trioxide and Cholecalciferol (Vitamin D) in Treating Patients With Myelodysplastic Syndromes
Phase II Trial of Arsenic Trioxide and Dose-Escalated Cholecalciferol in Myelodysplastic Syndrome

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.

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.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • 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
 
 

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
5
May 2010
January 2006   (final data collection date for primary outcome measure)

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
Both
 
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00104806
CDR0000415574, CCCWFU-29304, CCCWFU-BG04-452
No
Comprehensive Cancer Center of Wake Forest University
Comprehensive Cancer Center of Wake Forest University
National Cancer Institute (NCI)
Study Chair: Istvan Molnar, MD Comprehensive Cancer Center of Wake Forest University
Comprehensive Cancer Center of Wake Forest University
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP