Myelodysplastic SyndromePhase 2NCT01333449
Study of Decitabine Induction Prior to Allogeneic Hematopoietic Cell Transplant in Newly Diagnosed MDS Patients
A Phase 2 study testing Decitabine in people with Myelodysplastic Syndrome, run by Singapore General Hospital at 1 site in Singapore.
Trial summary
Allogeneic blood stem cell transplant remains the only potential curative treatment for myelodysplastic syndromes (MDS) to date. Pre-transplant induction chemotherapy with leukemia-type regimens is associated with significant toxicity and even death. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Decitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteSingapore
- Study dates
- Jul 2010to Aug 2013
- 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed MDS patients aged 21 to 65 years belonging to any of the following categories: refractory cytopenia with multilineage dysplasia (RCMD) with or without ringed sideroblasts (i.e. RCMD and RCMD-RS), refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2 if the prognostic scores are IPSS (international prognostic scoring system) Int-2 or IPSS-high or with WPSS (WHO prognostic scoring system) 3 and above
- Therapy-related MDS with IPSS Int-2 and above or WPSS 3
- Acceptable cardiac function MUGA or Echocardiography left ventricular ejection fraction of 40% and above
- Acceptable lung function: FEV1>70% predicted, DLCO>60% predicted
- Acceptable renal function: CCT > 50ml/min
- Acceptable liver function: abnormalities in bilirubin or transaminases not > 2times upper limit of normal
- Performance status of ECOG 2 or HCT-specific Comorbidity Index < 3
Who cannot join
- Any co-morbidity other than MDS which limits life-expectancy to <3mth
- Diagnosis of other active cancer other than squamous cell carcinoma, basal cell carcinoma or carcinoma-in-situ 1 or 2 of the cervix
- Presence of active infections not under control
- Receipt of 5-azacytidine or other induction chemotherapy for MDS/AML
- Patients not keen to explore allogeneic HCT as part of curative treatment plan
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Phase II Study of Decitabine Induction Therapy to Reduce Pre-transplant Disease Burden Prior to Allogeneic Hematopoietic Cell Transplant in Patients With Newly Diagnosed Myelodysplastic Syndromes.
Allogeneic blood stem cell transplant remains the only potential curative treatment for myelodysplastic syndromes (MDS) to date. Pre-transplant induction chemotherapy with leukemia-type regimens is associated with significant toxicity and even death. The hypomethylating agents decitabine and 5-azacytidine have been shown in studies to cause improved hematologic parameters and partial or complete responses in patients with high risk MDS compared to standard therapy. In contrast to leukemia-type chemotherapy, decitabine is associated with a relatively low risk of toxicity. We therefore propose to treat transplant-eligible MDS patients with Decitabine as induction therapy and a bridge to transplant.
Hypothesis:
- Decitabine is able to reduce disease burden as measured by blood and marrow blast counts prior to allogeneic hematopoietic stem cell transplant to below 5%.
- Decitabine is well-tolerated by patients with high-risk MDS and will be a safe induction agent and bridge prior to allogeneic transplant in transplant-eligible patients.
Read the detailed description
Primary endpoint:
- safety and tolerability of Decitabine prior to transplant (assessed by occurence of non-hematologic toxicities of grade 3 or more as defined by CTC grading)
- reduction in pre-transplant disease burden ability to achieve blast <5% in the bone marrow and peripheral blood
Secondary endpoints:
- Proportion of patients with suitable donor able to proceed to an allogeneic hematopoietic cell transplant.
- Non-relapse mortality
- time to neutrophil engraftment
- Overall survival and disease-free survival.
Patients will receive Decitabine until blast <5% is achieved, suitable HLA-matched donor or umbilical cord blood is available up to a maximum of 6 cycles. Patient who progress on therapy or are unable to find a donor by 6 cycles will be removed from protocol. The method, conditioning regimen and choice of donor will be determined based on patient's age and functional status, and transplant physician's discretion. The available regimens are standardized within the center
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Decitabine
- Keywords
- Decitabine, MDS, myelodysplastic syndrome, prospective open label, phaseII, Allogeneic Hematopoietic cell transplant
- Medical subject headings
- Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Decitabine 20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles. Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in pre-transplant disease burden
Measured: 2 years
Secondary outcomes (5)
Proportion of patients with suitable donor able to proceed to an allogeneic HCT
Measured: 2 years
Non-relapse mortality
Measured: 3 years
Time to neutrophil engraftment
Measured: 2 years
Overall survival survival
Measured: 3 years
Disease free survival
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2011 (estimated)
- Study startJul 2010
- Primary completionAug 2013
- Study completionAug 2013
Why it stopped: Poor subject accrual
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.
- More trials run by Singapore General HospitalThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Johnson & Johnson
- Responsible party
- Sponsor
- Investigators
- Aloysius Ho, Principal investigator, Singapore General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01333449
- Sponsor's protocol ID
- Decitabine01
- Status last verified
- Jun 2014
- First submitted
- 30 Nov 2010
- Last updated
- 17 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Phase II Study of Decitabine Induction Therapy to Reduce Pre-transplant Disease Burden Prior to Allogeneic Hematopoietic Cell Transplant in Patients With Newly Diagnosed Myelodysplastic Syndromes.
- ClinicalTrials.gov ID
- NCT01333449
- Acronym / sponsor ID
- Decitabine01
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Decitabine, MDS, myelodysplastic syndrome, prospective open label, phaseII, Allogeneic Hematopoietic cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor subject accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- Johnson & Johnson
- Study start
- Jul 2010
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 12 Apr 2011 (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.
Allogeneic blood stem cell transplant remains the only potential curative treatment for myelodysplastic syndromes (MDS) to date. Pre-transplant induction chemotherapy with leukemia-type regimens is associated with significant toxicity and even death. The hypomethylating agents decitabine and 5-azacytidine have been shown in studies to cause improved hematologic parameters and partial or complete responses in patients with high risk MDS compared to standard therapy. In contrast to leukemia-type chemotherapy, decitabine is associated with a relatively low risk of toxicity. We therefore propose to treat transplant-eligible MDS patients with Decitabine as induction therapy and a bridge to transplant.
Hypothesis:
- Decitabine is able to reduce disease burden as measured by blood and marrow blast counts prior to allogeneic hematopoietic stem cell transplant to below 5%.
- Decitabine is well-tolerated by patients with high-risk MDS and will be a safe induction agent and bridge prior to allogeneic transplant in transplant-eligible patients.
Detailed description
Primary endpoint:
- safety and tolerability of Decitabine prior to transplant (assessed by occurence of non-hematologic toxicities of grade 3 or more as defined by CTC grading)
- reduction in pre-transplant disease burden ability to achieve blast <5% in the bone marrow and peripheral blood
Secondary endpoints:
- Proportion of patients with suitable donor able to proceed to an allogeneic hematopoietic cell transplant.
- Non-relapse mortality
- time to neutrophil engraftment
- Overall survival and disease-free survival.
Patients will receive Decitabine until blast <5% is achieved, suitable HLA-matched donor or umbilical cord blood is available up to a maximum of 6 cycles. Patient who progress on therapy or are unable to find a donor by 6 cycles will be removed from protocol. The method, conditioning regimen and choice of donor will be determined based on patient's age and functional status, and transplant physician's discretion. The available regimens are standardized within the center
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: DecitabineDecitabine 20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Newly diagnosed MDS patients aged 21 to 65 years belonging to any of the following categories: refractory cytopenia with multilineage dysplasia (RCMD) with or without ringed sideroblasts (i.e. RCMD and RCMD-RS), refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2 if the prognostic scores are IPSS (international prognostic scoring system) Int-2 or IPSS-high or with WPSS (WHO prognostic scoring system) 3 and above
- Therapy-related MDS with IPSS Int-2 and above or WPSS 3
- Acceptable cardiac function MUGA or Echocardiography left ventricular ejection fraction of 40% and above
- Acceptable lung function: FEV1>70% predicted, DLCO>60% predicted
- Acceptable renal function: CCT > 50ml/min
Key exclusion criteria (6 listed)
- Any co-morbidity other than MDS which limits life-expectancy to <3mth
- Diagnosis of other active cancer other than squamous cell carcinoma, basal cell carcinoma or carcinoma-in-situ 1 or 2 of the cervix
- Presence of active infections not under control
- Receipt of 5-azacytidine or other induction chemotherapy for MDS/AML
- Patients not keen to explore allogeneic HCT as part of curative treatment plan
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 |
|---|---|---|
| DecitabineAlso: Dacogen20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles. | Drug | Single Arm |
Primary outcome
Reduction in pre-transplant disease burden
Time frame: 2 years
5 secondary outcomes
Proportion of patients with suitable donor able to proceed to an allogeneic HCT
Time frame: 2 years
Non-relapse mortality
Time frame: 3 years
Time to neutrophil engraftment
Time frame: 2 years
Overall survival survival
Time frame: 3 years
Disease free survival
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Poor subject accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2014.
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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.
Aloysius Ho principal investigator
Singapore General Hospital
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 in people with Myelodysplastic Syndrome, run by Singapore General Hospital at 1 site in Singapore.
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 7 inclusion and 6 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: stopped early, as of the sponsor's last update on 17 Jun 2014. 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 Singapore. 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 was stopped early (reason given: Poor subject accrual). Results are not available in the source record.
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?
Reduction in pre-transplant disease burden (time frame: 2 years). 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 17 Jun 2014.