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

This study has been terminated.
(sponsor discontinues support)
Sponsor:
Collaborator:
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
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Dietary Supplement: cholecalciferol
Drug: arsenic trioxide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Arsenic Trioxide and Dose-Escalated Cholecalciferol in Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • 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 ]

Enrollment: 5
Study Start Date: November 2004
Study Completion Date: May 2010
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00104806

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Study Chair: Istvan Molnar, MD Comprehensive Cancer Center of Wake Forest University
  More Information

No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00104806     History of Changes
Other Study ID Numbers: CDR0000415574, CCCWFU-29304, CCCWFU-BG04-452
Study First Received: March 3, 2005
Last Updated: July 12, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
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

Additional relevant MeSH terms:
Neoplasms
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cholecalciferol
Arsenic trioxide
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014