Clinical trial NCT00104806: Arsenic Trioxide and Cholecalciferol (Vitamin D) in Treating Patients With Myelodysplastic Syndromes
Official title: Phase II Trial of Arsenic Trioxide and Dose-Escalated Cholecalciferol in Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Keywords: 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
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-03-04
Enrollment: 5
Sex: ALL
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Complete response rate
timeFrame: 6 months
measure: toxicity assessment after therapy
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Istvan Molnar, MD
role: STUDY_CHAIR
References: