Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Myelofibrosis/Myeloproliferative Disorder

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00274820

Collaborator

(none)

Enrollment

Locations

Duration (Months)

7.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of cancer cells. The cancer is said to be resistant to chemotherapy. Giving ascorbic acid may reduce drug resistance and allow the cancer cells to be killed. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with ascorbic acid, dexamethasone, and thalidomide works in treating patients with chronic idiopathic myelofibrosis or myelodysplastic or myeloproliferative disorders.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Dietary Supplement: ascorbic acid Drug: arsenic trioxide Drug: dexamethasone Drug: thalidomide	Phase 2

Detailed Description

OBJECTIVES:

Primary

Evaluate the efficacy (in terms of response rate) of arsenic trioxide, ascorbic acid, dexamethasone, and thalidomide in patients with chronic idiopathic myelofibrosis or myelodysplastic/myeloproliferative disorders.

Secondary

Determine the rate of disease progression or progression to acute leukemia in patients treated with this regimen.
Assess improvement in bone marrow pathology (including degree of fibrosis, percentage of blasts, and resolution of cytogenetic abnormalities) in patients treated with this regimen.
Determine time to response in patients treated with this regimen.
Determine the reduction of spleen size in patients treated with this regimen.
Measure clinical responses and quality of life in subgroups treated with this regimen.
Determine the safety of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive arsenic trioxide IV over 1-2 hours for 5 days and oral ascorbic acid once daily for 5 days during week 1. Patients then receive arsenic trioxide and ascorbic acid twice a week in weeks 2-12. Patients also receive oral dexamethasone once daily for 5 days in weeks 1, 5, 9, and 12 and oral thalidomide once or twice daily in weeks 1-12. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and after every course.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Combination Therapy With Thalidomide, Arsenic Trioxide, Dexamethasone, and Ascorbic Acid (TADA) in Patients With Chronic Idiopathic Myelofibrosis or Overlap Myelodysplastic/Myeloproliferative Disorders

Study Start Date :

Oct 1, 2005

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

Response rate at 6 months [at 6months of therapy and followed for at least 4 weeks after]
Patients with any improvement in disease status (hematologic improvement or partial remission for patients with higher risk disease) may continue on study until a major response or complete remission occurs. Study visits will occur weekly for the first four weeks, then every four weeks, for each cycle. Laboratory monitoring to assess hematological parameters will occur weekly for the first four weeks, then every four weeks, for each cycle.

Secondary Outcome Measures

Bone marrow response at 6 months [at 6 months]
Bone marrow aspirate / biopsy for morphology and blast count, iron stain and cytogenetics.
Spleen size at 12 weeks [at 12 weeks]
Ultrasound of the spleen
Quality of life [every 12 weeks]
Patients will complete the FACT-An questionnaire every 12 weeks.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Chronic idiopathic myelofibrosis or myelodysplastic/myeloproliferative disorders (MDS/MPD), including the following subtypes:
Chronic idiopathic myelofibrosis (with extramedullary hematopoiesis)
Chronic myelomonocytic leukemia (CMML)
Atypical chronic myeloid leukemia
MDS/MPD disease, unclassifiable
MDS with ≥ 2+ fibrosis present in the bone marrow
Patients with MPD must be negative by fluorescent in situ hybridization (FISH) for the BCR/ABL fusion gene

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy of at least 3 months
Platelet count > 10,000/mm³
Bilirubin ≤ 2.5 times upper limit of normal (ULN)
SGOT and SGPT ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Potassium ≥ 4.0 mEq/dL (supplemental electrolytes allowed)
Magnesium > 1.8 mg/dL (supplemental electrolytes allowed)
Absolute QTc interval < 460 msec
Patients who have a QT > 460 after electrolyte repletion and discontinuation of other unessential QT-prolonging drugs will be excluded
Negative pregnancy test
Women of childbearing potential must use medically acceptable birth control (two methods of birth control or at least one highly active method and one additional effective method), starting 4 weeks prior to starting thalidomide, all through thalidomide therapy, and for 4 weeks after discontinuing thalidomide
Male patients with reproductive potential must use a latex condom every time they have sex with a woman from the time that they start taking thalidomide, all through thalidomide therapy, and for 4 weeks after discontinuing thalidomide
No sperm or blood donation during study treatment
Must be willing and able to comply with the FDA-mandated System for Thalidomide Educational Prescribing and Safety (S.T.E.P.S™) program
No other serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the patient at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent
No preexisting neurotoxicity/neuropathy ≥ grade 2
Not pregnant or nursing
No cardiac conduction defects
No unstable angina
No myocardial infarction within the past 6 months
No congestive heart failure of any cause
No New York Heart Association class II or greater
No other significant underlying cardiac dysfunction
No prior malignancy in the 3 years before treatment in this study (other than curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer)
No sulfa allergy that would interfere with administration of trimethoprim sulfamethoxazole prophylaxis
Patients with sulfa allergies who could instead receive pentamidine prophylaxis also will be excluded
Patients with sulfa allergies who can instead receive atovaquone may be included

PRIOR CONCURRENT THERAPY:

At least 4 weeks since prior investigational or approved therapy for this disease
No growth factors within 1 week of study enrollment
No other concurrent cytotoxic drugs or other investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
2	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195