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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate at 6 months

Outcome Description:

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.

Outcome Time Frame:

at 6months of therapy and followed for at least 4 weeks after

Safety Issue:

No

Principal Investigator

Mikkael A. Sekeres, MD, MS

Investigator Role:

Study Chair

Investigator Affiliation:

The Cleveland Clinic

Authority:

United States: Food and Drug Administration

Study ID:

CASE4Y04

NCT ID:

NCT00274820

Start Date:

October 2005

Completion Date:

October 2007

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • chronic idiopathic myelofibrosis
  • chronic myelomonocytic leukemia
  • atypical chronic myeloid leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Primary Myelofibrosis
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Cleveland, Ohio  44195