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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00274820
First received: January 10, 2006
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response rate at 6 months [ Time Frame: at 6months of therapy and followed for at least 4 weeks after ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
    Bone marrow aspirate / biopsy for morphology and blast count, iron stain and cytogenetics.

  • Spleen size at 12 weeks [ Time Frame: at 12 weeks ] [ Designated as safety issue: No ]
    Ultrasound of the spleen

  • Quality of life [ Time Frame: every 12 weeks ] [ Designated as safety issue: No ]
    Patients will complete the FACT-An questionnaire every 12 weeks.


Enrollment: 15
Study Start Date: October 2005
Study Completion Date: October 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Dietary Supplement: ascorbic acid
    The dose of ascorbic acid will be 1000 mg PO 2-3 hours prior to ATO infusion. The treatment will follow the same schedule as arsenic trioxide.
    Other Name: vitamin C
    Drug: arsenic trioxide
    Treatment consists of a loading period of five 0.25 mg/kg ATO doses in the first week, followed by maintenance dosing with 0.25 mg/kg ATO twice weekly for 11 weeks. Loading is usually done Monday through Friday of the first treatment week. Maintenance should be started either 72 or 96 hours after the last loading dose. Thereafter, dosing is twice weekly, following an alternating pattern of 72 and 96 hours. For example, maintenance dosing may be done on Mondays and Thursdays, Tuesdays and Fridays, etc. The same pattern should be followed for the entire maintenance dosing period.
    Other Names:
    • Trisenox®
    • ATO
    Drug: dexamethasone
    Dexamethasone will be given at a dose of 4mg PO daily for five days every four weeks (i.e., days 1-5, 29-33, 57-61, 84-88, etc.).
    Drug: thalidomide
    The dose of thalidomide will be 50 mg PO daily starting day 1. The dose will be increased to 100mg PO daily after two weeks if tolerated and only if patients experience < grade 1 thalidomide-attributed toxicity using CTC criteria.
    Other Name: Thalomid®
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274820

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: Mikkael A. Sekeres, MD, MS The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00274820     History of Changes
Other Study ID Numbers: CASE4Y04, P30CA043703, CCF-7671, CASE4Y04
Study First Received: January 10, 2006
Last Updated: September 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Primary Myelofibrosis
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Precancerous Conditions
Ascorbic Acid
Thalidomide
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Arsenic trioxide
BB 1101
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamins
Micronutrients
Growth Substances
Anti-Inflammatory Agents
Therapeutic Uses
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on July 22, 2014