Myelodysplastic SyndromePhase 2NCT01652781
5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome
A Phase 2 study testing Azacitidine in people with Myelodysplastic Syndrome, run by Seoul St. Mary's Hospital at 3 sites in South Korea.
Trial summary
Approved dosing schedule of azacitidine for myelodysplastic syndrome (MDS) is 75 mg/m^2/day subcutaneous for 7 consecutive days every 28 days, which is based on the data from standard chemotherapy regimen and a Phase I safety clinical trial. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 3 sitesSouth Korea
- Study dates
- Mar 2012to Dec 2016
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria in order to be enrolled in this clinical trial: Patients who have been diagnosed with MDS by the FAB criteria and belong to Low or INT-1 risk by the IPSS classification will be enrolled in this study. For the purpose of analysis, chronic myelomonocytic leukemia (CMML) patients with less than 5% of myeloblasts are also classified by the IPSS risk classification. Secondary or treatment-related MDS is allowed, but recurrent or persistent MDS after stem cell is not applicable. The enrolled patients should have anemia (hemoglobin < 10.0g/dL), transfusion dependence, thrombocytopenia (less than 100×10^9/L), or absolute neutrophil count less than 1.80×10^9/L.
- 18 years of age or older
- Life expectancy of at least 12 months
- ECOG performance status 2 or less
- Serum creatinine less than 1.5 times the upper limit of normal (ULN) level of the investigating institution
- Serum bilirubin less than 2.0 times the upper limit of normal (ULN) level of the investigating institution
Show all 10Show fewer
- AST, ALT, and alkaline phosphatase less than 3 times the upper limit of normal (ULN) level of the investigation institution
- Patients who can have informed consent and signed the informed consent form
- Male patients who have a female partner of childbearing potential must agree to use two types of effective contraceptive methods during the study and for 30 days following the last dose.
- Females of childbearing potential (FCBP) must satisfy the following criteria: must agree to use the contraceptive method (oral contraceptives, injectables, hormonal implants; tubal ligation; intra uterine device; spermicidal contraceptives, the sterilized partner) approved by the physician during azacitidine treatment and for 3 months following the last dose, and must have a negative result of serum pregnancy test that was performed within 72 hours prior to starting study drug therapy.
Who cannot join
- Any coexisting major illness or organ failure
- HIV positive, or active hepatitis B or C infection
- Uncontrolled acute infection
- Uncontrolled hemorrhage
- Pregnant or lactating
- Known or suspected hypersensitivity to azacitidine
- Patients diagnosed with malignant hepatic carcinoma or malignant disease within the past 12 months (except in situ carcinoma without complication, cervical or breast intraepithelial neoplasia, or other local malignant carcinoma that is likely to be treated by surgical removal or radiotherapy)
Trial locations and contacts
3 sites in 1 country.
South Korea3 sites, 3 recruiting
- Recruiting
Seoul St. Mary's Hospital
Seoul, 137-701
Yoo-Jin Kim, MD, PhD, 82-2-2258-6057, yoojink@catholic.ac.kr
Kyungmin Kim, 82-2-2258-7926, ddok9765@hotmail.com
- Recruiting
Asan Medical Center
Seoul
Je Hwan Lee, MD, PhD
- Recruiting
Seoul National University Hospital
Seoul
Sung Soo Yoon, MD, PhD
About this study
Official title: A Randomized, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of 5-day Azacitidine for Patients With Lower-risk Myelodysplastic Syndrome
Approved dosing schedule of azacitidine for myelodysplastic syndrome (MDS) is 75 mg/m^2/day subcutaneous for 7 consecutive days every 28 days, which is based on the data from standard chemotherapy regimen and a Phase I safety clinical trial. Since the optimal dosage of this drug has not been found yet, it remains as a subject of clinical study that needs to be examined. If initial toxicity is minimized by developing dosage/regimen that replaces the standard therapy, it will be possible to provide continuous treatment with increased convenience by patients and treating physicians as well as improvement for safety in elderly patients or those with serious cytopenia. In addition, it is expected to lead to a better response by strictly keeping a treatment schedule.
Recent US study showed that 5-day regimen showed similar treatment results, but retrospective data from Spain showed lower response rate in 5-day regimen. Considering the recent circumstances around dosage and schedule of azacitidine in lower risk MDS, a Phase II clinical trial is planned in lower risk MDS patients in order to explore the efficacy in 5-day treatment by comparing prospectively with 7-day standard regimen.
Read the detailed description
- Using block randomization, subjects of Low or intermediate (INT)-1 patients will be equally allocated to the following two types of regimens.
- Group A: azacitidine 75mg/m^2 subcutaneously for 7 days every 28 days + best supportive care
- Group B: azacitidine 75mg/m^2 subcutaneously for 5 days every 28 days + best supportive care
- The study drug, azacitidine, is provided free of charge by Celgene until disease progression or relapse after response, or intolerable toxicity occurs in clinical study subject, or informed consent is withdrawn.
- No crossover between arms is allowed.
- Dose escalation in this study is not allowed; on the contrary, dose reduction or dose delay is possible based on adverse events and hematologic recovery.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Azacitidine
- Keywords
- myelodysplastic syndrome, azacitidine, dosing schedule
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called vidaza
5-day arm: azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care 7-day arm: azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care
| Study group | Role | What they receive |
|---|---|---|
| 5-day arm | Experimental | azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care Receives: Drug: Azacitidine |
| 7-day arm | Active comparator | azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate by modified IWG 2006 response criteria
Overall response rate is evaluated by assessing the percentage of patients with response (complete remission (CR), partial remission (PR), bone marrow CR, and hematologic improvement), response period, and transfusion requirement. Best response during at least 6 cycles of treatment will be assessed if there is no treatment failure or disease progression within 6 cycles of treatment. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.
Measured: After 6 cycles of treatment up to 25-49 weeks
Secondary outcomes (2)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
•Safety and tolerability profile of 5-day azacitidine in comparison with 7-day regimen. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.
Measured: After each course of treatment up to 25-49 weeks
Cytogenetic response rate by IWG 2006 response criteria
•Cytogenetic response of of 5-day azacitidine in comparison with 7-day regimen. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.
Measured: After 6 cycles of treatment up to 25-49 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2012 (estimated)
- Study startMar 2012
- Primary completionJun 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul St. Mary's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Principal investigator, Yoo-Jin Kim, Seoul St. Mary's Hospital
- Investigators
- Yoo-Jin Kim, MD, PhD, Principal investigator, Division of hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01652781
- Sponsor's protocol ID
- VZ-MDS-PI-0267
- Status last verified
- Nov 2015
- First submitted
- 11 Jul 2012
- Last updated
- 20 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of 5-day Azacitidine for Patients With Lower-risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT01652781
- Acronym / sponsor ID
- VZ-MDS-PI-0267
- Conditions
- Myelodysplastic Syndrome
- Keywords
- myelodysplastic syndrome, azacitidine, dosing schedule
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Seoul St. Mary's HospitalUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Mar 2012
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 30 Jul 2012 (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.
Approved dosing schedule of azacitidine for myelodysplastic syndrome (MDS) is 75 mg/m^2/day subcutaneous for 7 consecutive days every 28 days, which is based on the data from standard chemotherapy regimen and a Phase I safety clinical trial. Since the optimal dosage of this drug has not been found yet, it remains as a subject of clinical study that needs to be examined. If initial toxicity is minimized by developing dosage/regimen that replaces the standard therapy, it will be possible to provide continuous treatment with increased convenience by patients and treating physicians as well as improvement for safety in elderly patients or those with serious cytopenia. In addition, it is expected to lead to a better response by strictly keeping a treatment schedule.
Recent US study showed that 5-day regimen showed similar treatment results, but retrospective data from Spain showed lower response rate in 5-day regimen. Considering the recent circumstances around dosage and schedule of azacitidine in lower risk MDS, a Phase II clinical trial is planned in lower risk MDS patients in order to explore the efficacy in 5-day treatment by comparing prospectively with 7-day standard regimen.
Detailed description
- Using block randomization, subjects of Low or intermediate (INT)-1 patients will be equally allocated to the following two types of regimens.
- Group A: azacitidine 75mg/m^2 subcutaneously for 7 days every 28 days + best supportive care
- Group B: azacitidine 75mg/m^2 subcutaneously for 5 days every 28 days + best supportive care
- The study drug, azacitidine, is provided free of charge by Celgene until disease progression or relapse after response, or intolerable toxicity occurs in clinical study subject, or informed consent is withdrawn.
- No crossover between arms is allowed.
- Dose escalation in this study is not allowed; on the contrary, dose reduction or dose delay is possible based on adverse events and hematologic recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5-day arm | Experimental | Drug: Azacitidineazacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care |
| 7-day arm | Active comparator | Drug: Azacitidineazacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must satisfy the following criteria in order to be enrolled in this clinical trial: Patients who have been diagnosed with MDS by the FAB criteria and belong to Low or INT-1 risk by the IPSS classification will be enrolled in this study. For the purpose of analysis, chronic myelomonocytic leukemia (CMML) patients with less than 5% of myeloblasts are also classified by the IPSS risk classification. Secondary or treatment-related MDS is allowed, but recurrent or persistent MDS after stem cell is not applicable. The enrolled patients should have anemia (hemoglobin < 10.0g/dL), transfusion dependence, thrombocytopenia (less than 100×10^9/L), or absolute neutrophil count less than 1.80×10^9/L.
- 18 years of age or older
- Life expectancy of at least 12 months
- ECOG performance status 2 or less
- Serum creatinine less than 1.5 times the upper limit of normal (ULN) level of the investigating institution
Key exclusion criteria (7 listed)
- Any coexisting major illness or organ failure
- HIV positive, or active hepatitis B or C infection
- Uncontrolled acute infection
- Uncontrolled hemorrhage
- Pregnant or lactating
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 |
|---|---|---|
| AzacitidineAlso: vidaza5-day arm: azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care 7-day arm: azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care | Drug | 5-day arm, 7-day arm |
Primary outcome
Overall response rate by modified IWG 2006 response criteria
Time frame: After 6 cycles of treatment up to 25-49 weeks
Overall response rate is evaluated by assessing the percentage of patients with response (complete remission (CR), partial remission (PR), bone marrow CR, and hematologic improvement), response period, and transfusion requirement. Best response during at least 6 cycles of treatment will be assessed if there is no treatment failure or disease progression within 6 cycles of treatment. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.
2 secondary outcomes
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: After each course of treatment up to 25-49 weeks
Cytogenetic response rate by IWG 2006 response criteria
Time frame: After 6 cycles of treatment up to 25-49 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
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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.
Yoo-Jin Kim, MD, PhD principal investigator
Division of hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital
3 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 Azacitidine in people with Myelodysplastic Syndrome, run by Seoul St. Mary's Hospital at 3 sites in South Korea.
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 10 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Korea. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yoo-Jin Kim, MD, PhD (82-2-2258-6057, yoojink@catholic.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate by modified IWG 2006 response criteria (time frame: After 6 cycles of treatment up to 25-49 weeks). 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 20 Nov 2015.