Myelodysplastic SyndromePhase 2NCT00621023
Cephalon Decitabine, Arsenic Trioxide and Ascorbic Acid for Myelodysplastic Syndrome
A Phase 2 study testing Decitabine, Arsenic Trioxide and Ascorbic Acid in people with Myelodysplastic Syndrome, run by Duke University at 1 site in United States.
Trial summary
This will be an open-label, non-randomized trial pilot phase II trial open to patients with myelodysplastic syndrome. The purpose of the study is to find out if the combination of decitabine, arsenic trioxide and ascorbic acid is safe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Decitabine, Arsenic Trioxide and Ascorbic Acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Apr 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Established diagnosis of MDS (de novo or secondary) fitting either the French American British Cooperative Group (FAB) or World Health Organization (WHO) classification systems as determined by a complete blood count (CBC) and bone marrow biopsy. Patients with >20% bone marrow blasts but <30% bone marrow blasts who would be classified as refractory anemia with excess blasts (RAEB-t) in the FAB and acute myeloid leukemia (AML) in the WHO systems are still eligible for this study. Patients with low risk MDS (IPSS scores low or intermediate -1 (INT-1) must be transfusion dependent to be eligible. Transfusion dependent will be defined as having 2 or more transfusion events within a 90 day period.
- Eastern Oncology Cooperative Group (ECOG) or WHO performance status of 0-2 (Appendix)
- Able to provide written informed consent.
Who cannot join
- Pregnant females
- AML defined as > 30% bone marrow blasts.
- Any malignant disease within the past 2 years, except cervical carcinoma, basal cell carcinoma of the skin, and squamous cell carcinoma of the skin..
- Off all prior treatment for MDS for at least 4 weeks from entry.
- Off any investigational agents for at least 4 weeks from entry.
- Uncontrolled cardiac disease or congestive heart failure as defined by New York Heart Association criteria of Class III or greater.
Show all 10Show fewer
- Uncontrolled pulmonary disease.
- Uncontrolled or active viral or bacterial infection. All infections must have been fully treated with antibiotics.
- HIV +
- Lab values as specified in the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Pilot Phase II Study of Decitabine, Arsenic Trioxide and Ascorbic Acid for Patients With Myelodysplastic Syndrome
This will be an open-label, non-randomized trial pilot phase II trial open to patients with myelodysplastic syndrome. The purpose of the study is to find out if the combination of decitabine, arsenic trioxide and ascorbic acid is safe.
Read the detailed description
Conventional therapy for MDS has been poor at best. Supportive care with transfusion therapy and antibiotics have remained an option for all patients with myelodysplastic syndrome (MDS).
The only known curative therapy is an allogeneic bone marrow transplant. However due to its high morbidity in this elderly population and the lack of available donors, it is estimated that less than 5% of patients with MDS are candidates for this type of aggressive therapy. Investigational therapies are thus warranted in MDS.
Decitabine shows significant clinical activity in patients with MDS, with moderate toxicity. The major toxicity is myelosuppression with subsequent infection occurring in 20-25% of patients.
Arsenic trioxide is an FDA approved drug for the treatment of patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. Two pivotal studies of arsenic trioxide in the setting of relapsed APL showed a complete remission rate of 87% with a 36 month survival estimate of 50%. As of May 2004, over 800 patients had received arsenic trioxide in clinical studies or through a compassionate use program, and an additional 3600 patients had received the drug in clinical practice.
Arsenic trioxide shows clinical activity in MDS. Side effects have been noted and are manageable.
Adult patients with an established diagnosis of MDS will receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. The dose of ascorbic acid will be 1000 mg in 100 mL a solution of 5% dextrose in water (D5W) (protected from light and air) administered as an IV infusion over 15 to 30 minutes and administered within 30 minutes after arsenic trioxide administration.
Each cycle will consist of 4 weeks of treatment, and patients will be assessed each cycle for toxicity, and after 4 cycles for response as defined by the International Working Group (IWG - see section 8.0). Patients will have transfusion and supportive care therapy administered per the treating physician's discretion.
Patients with a response (complete response - CR, partial remission - PR, or hematologic improvement) after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Decitabine, Arsenic Trioxide and Ascorbic Acid
- Keywords
- Myelodysplastic syndrome, MDS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Decitabine, Arsenic Trioxide and Ascorbic AcidDrug
Also called Decitabine, ATO
Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Receives: Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR)
Complete response and Partial response are defined using 2000 international working group (IWG) criteria. The Primary criteria for a CR is a repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia . A PR meets all the CR criteria except Blasts decreased by >50% over pretreatment, or a less advanced myelodysplastic syndrome (MDS) French American British (FAB) classification than pretreatment.
Measured: after 4 cycles of therapy
Secondary outcomes (2)
Duration of a Complete or Partial Response Based on Number of People Who Responded.
Number of months a complete or partial response was maintained.
Measured: Up to 5 years or until death
Number of Patients With an Unacceptable Toxicity
Any of the following non-hematologic toxicities that causes a patient's therapy to be suspended or discontinued: Creatinine > 2x baseline value; serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), Total bilirubin > 2x the upper limit of normal; Febrile neutropenia; Uncontrolled infection; Hepatotoxicity defined as an increase in serum bilirubin, SGOT, or alkaline phosphatase to >5 times baseline value); nephrotoxicity (defined as serum creatinine >3.5 times the ULN); neurological impairment (defined as somnolence, seizures, or impaired mentation); severe peripheral neuropathy, or any non-hematologic grade 4 toxic event.
Measured: During the treatment period and for 30 days after last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2008 (estimated)
- Study startNov 2007
- Primary completionApr 2010
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Cephalon, Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- Carlos de Castro, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00621023
- Sponsor's protocol ID
- Pro00011792
- Other IDs
- 7667A
- Status last verified
- Jan 2013
- First submitted
- 26 Dec 2007
- Last updated
- 4 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase II Study of Decitabine, Arsenic Trioxide and Ascorbic Acid for Patients With Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT00621023
- Acronym / sponsor ID
- Pro00011792
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Myelodysplastic syndrome, MDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Cephalon, Eisai Inc.
- Study start
- Nov 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 22 Feb 2008 (estimated)
- Results
- Posted 28 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be an open-label, non-randomized trial pilot phase II trial open to patients with myelodysplastic syndrome. The purpose of the study is to find out if the combination of decitabine, arsenic trioxide and ascorbic acid is safe.
Detailed description
Conventional therapy for MDS has been poor at best. Supportive care with transfusion therapy and antibiotics have remained an option for all patients with myelodysplastic syndrome (MDS).
The only known curative therapy is an allogeneic bone marrow transplant. However due to its high morbidity in this elderly population and the lack of available donors, it is estimated that less than 5% of patients with MDS are candidates for this type of aggressive therapy. Investigational therapies are thus warranted in MDS.
Decitabine shows significant clinical activity in patients with MDS, with moderate toxicity. The major toxicity is myelosuppression with subsequent infection occurring in 20-25% of patients.
Arsenic trioxide is an FDA approved drug for the treatment of patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. Two pivotal studies of arsenic trioxide in the setting of relapsed APL showed a complete remission rate of 87% with a 36 month survival estimate of 50%. As of May 2004, over 800 patients had received arsenic trioxide in clinical studies or through a compassionate use program, and an additional 3600 patients had received the drug in clinical practice.
Arsenic trioxide shows clinical activity in MDS. Side effects have been noted and are manageable.
Adult patients with an established diagnosis of MDS will receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. The dose of ascorbic acid will be 1000 mg in 100 mL a solution of 5% dextrose in water (D5W) (protected from light and air) administered as an IV infusion over 15 to 30 minutes and administered within 30 minutes after arsenic trioxide administration.
Each cycle will consist of 4 weeks of treatment, and patients will be assessed each cycle for toxicity, and after 4 cycles for response as defined by the International Working Group (IWG - see section 8.0). Patients will have transfusion and supportive care therapy administered per the treating physician's discretion.
Patients with a response (complete response - CR, partial remission - PR, or hematologic improvement) after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Decitabine, Arsenic Trioxide and Ascorbic AcidDrug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Established diagnosis of MDS (de novo or secondary) fitting either the French American British Cooperative Group (FAB) or World Health Organization (WHO) classification systems as determined by a complete blood count (CBC) and bone marrow biopsy. Patients with >20% bone marrow blasts but <30% bone marrow blasts who would be classified as refractory anemia with excess blasts (RAEB-t) in the FAB and acute myeloid leukemia (AML) in the WHO systems are still eligible for this study. Patients with low risk MDS (IPSS scores low or intermediate -1 (INT-1) must be transfusion dependent to be eligible. Transfusion dependent will be defined as having 2 or more transfusion events within a 90 day period.
- Eastern Oncology Cooperative Group (ECOG) or WHO performance status of 0-2 (Appendix)
- Able to provide written informed consent.
Key exclusion criteria (10 listed)
- Pregnant females
- AML defined as > 30% bone marrow blasts.
- Any malignant disease within the past 2 years, except cervical carcinoma, basal cell carcinoma of the skin, and squamous cell carcinoma of the skin..
- Off all prior treatment for MDS for at least 4 weeks from entry.
- Off any investigational agents for at least 4 weeks from entry.
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 |
|---|---|---|
| Decitabine, Arsenic Trioxide and Ascorbic AcidAlso: Decitabine, ATOSubjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles. | Drug | 1 |
Primary outcome
Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR)
Time frame: after 4 cycles of therapy
Complete response and Partial response are defined using 2000 international working group (IWG) criteria. The Primary criteria for a CR is a repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia . A PR meets all the CR criteria except Blasts decreased by >50% over pretreatment, or a less advanced myelodysplastic syndrome (MDS) French American British (FAB) classification than pretreatment.
2 secondary outcomes
Duration of a Complete or Partial Response Based on Number of People Who Responded.
Time frame: Up to 5 years or until death
Number of Patients With an Unacceptable Toxicity
Time frame: During the treatment period and for 30 days after last dose of study drug
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Carlos de Castro, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Decitabine, Arsenic Trioxide and Ascorbic Acid in people with Myelodysplastic Syndrome, run by Duke University at 1 site 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?
The sponsor lists 3 inclusion and 10 exclusion criteria. 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 4 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 28 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR) (time frame: after 4 cycles of therapy). 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 4 Feb 2013.