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

August 8, 2018 updated by: Wake Forest University Health Sciences

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- North Carolina
  - Winston-Salem, North Carolina, United States, 27157-1096
    - Wake Forest University Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response rate Time Frame: 6 months	6 months
toxicity assessment after therapy Time Frame: 28 days	28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2004

Primary Completion (Actual)

January 1, 2006

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

March 3, 2005

First Submitted That Met QC Criteria