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

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ascorbic acid
arsenic trioxide
dexamethasone
thalidomide
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

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

Full Information

First Posted
January 10, 2006
Last Updated
July 23, 2020
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00274820
Brief Title
Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Myelofibrosis/Myeloproliferative Disorder
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 Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
October 2005 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
October 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Dietary Supplement
Intervention Name(s)
ascorbic acid
Other Intervention Name(s)
vitamin C
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
arsenic trioxide
Other Intervention Name(s)
Trisenox®, ATO
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
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.).
Intervention Type
Drug
Intervention Name(s)
thalidomide
Other Intervention Name(s)
Thalomid®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Response rate at 6 months
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.
Time Frame
at 6months of therapy and followed for at least 4 weeks after
Secondary Outcome Measure Information:
Title
Bone marrow response at 6 months
Description
Bone marrow aspirate / biopsy for morphology and blast count, iron stain and cytogenetics.
Time Frame
at 6 months
Title
Spleen size at 12 weeks
Description
Ultrasound of the spleen
Time Frame
at 12 weeks
Title
Quality of life
Description
Patients will complete the FACT-An questionnaire every 12 weeks.
Time Frame
every 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikkael A. Sekeres, MD, MS
Organizational Affiliation
The Cleveland Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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