Chronic Myeloproliferative DisordersPhase 2NCT00274820
Arsenic Trioxide, Ascorbic Acid, Dexamethasone, and Thalidomide in Myelofibrosis/Myeloproliferative Disorder
A Phase 2 study testing ascorbic acid, arsenic trioxide and dexamethasone in people with Chronic Myeloproliferative Disorders and Leukemia, run by Case Comprehensive Cancer Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes
- What is being tested?
- ascorbic acid, arsenic trioxide and dexamethasone
- Type of treatment
- Injection or infusion
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2005to Oct 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
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
About this study
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
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.
Read the 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.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Being tested
- ascorbic acid, arsenic trioxide, dexamethasone, thalidomide
- 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
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Primary Myelofibrosis, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ascorbic acidDietary supplement
Also called vitamin C
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.
arsenic trioxideDrug
Also called Trisenox®, ATO
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.
dexamethasoneDrug
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.).
thalidomideDrug
Also called Thalomid®
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at 6months of therapy and followed for at least 4 weeks after
Secondary outcomes (3)
Bone marrow response at 6 months
Bone marrow aspirate / biopsy for morphology and blast count, iron stain and cytogenetics.
Measured: at 6 months
Spleen size at 12 weeks
Ultrasound of the spleen
Measured: at 12 weeks
Quality of life
Patients will complete the FACT-An questionnaire every 12 weeks.
Measured: every 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2006 (estimated)
- Study startOct 2005
- Primary completionSep 2007
- Study completionOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mikkael A. Sekeres, MD, MS, Study chair, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00274820
- Sponsor's protocol ID
- CASE4Y04
- Status last verified
- Jul 2020
- First submitted
- 10 Jan 2006
- Last updated
- 27 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00274820
- Acronym / sponsor ID
- CASE4Y04
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Oct 2005
- Primary completion
- Sep 2007 (actual)
- Study completion
- Oct 2007 (actual)
- First posted
- 11 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ascorbic acidAlso: vitamin CThe 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. | Dietary supplement | – |
| arsenic trioxideAlso: Trisenox®, ATOTreatment 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. | Drug | – |
| dexamethasoneDexamethasone 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 | – |
| thalidomideAlso: Thalomid®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. | Drug | – |
Primary outcome
Response rate at 6 months
Time frame: 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.
3 secondary outcomes
Bone marrow response at 6 months
Time frame: at 6 months
Spleen size at 12 weeks
Time frame: at 12 weeks
Quality of life
Time frame: every 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikkael A. Sekeres, MD, MS study chair
The Cleveland Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ascorbic acid, arsenic trioxide and dexamethasone in people with Chronic Myeloproliferative Disorders and Leukemia, run by Case Comprehensive Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate at 6 months (time frame: at 6months of therapy and followed for at least 4 weeks after). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2020; AzTrials last refreshed its copy on 8 Nov 2026.