Phase II Trial of Arsenic Trioxide and Dose-Escalated Cholecalciferol in Myelodysplastic Syndrome
N/A
N/A
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
Phase II Trial of Arsenic Trioxide and Dose-Escalated Cholecalciferol in Myelodysplastic Syndrome
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete response rate
Outcome Time Frame:
6 months
Safety Issue:
No
Principal Investigator
Istvan Molnar, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Comprehensive Cancer Center of Wake Forest University
Authority:
United States: Institutional Review Board
Study ID:
CDR0000415574
NCT ID:
NCT00104806
Start Date:
November 2004
Completion Date:
May 2010
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- 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
- Neoplasms
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
