Stem Cell Transplant ComplicationsPhase 2/3NCT03799224
Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia
A Phase 2/3 study testing Decitabine, mBU/CY and ATG and mBU/CY in people with Stem Cell Transplant Complications and Relapse Leukemia, run by Peking University People's Hospital at 1 site in China.
Trial summary
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly causes of transplant failure. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Stem Cell Transplant Complications, Relapse Leukemia, Refractory Leukemia
- What is being tested?
- Decitabine, mBU/CY and ATG and mBU/CY
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2018to 31 Dec 2023
- Phase
- Phase 2/3
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- patients with relapsed acute leukemia
- patients with acute leukemia in the third（or more）complete remission (CR3) status
Who cannot join
- pregnancy women
- uncontrolled severe infection
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking University Institute of Hematology,Beijing
Beijing, Beijing Municipality, 100044
Chen-hua Yan, MD, 86 010 88326666, yanchenhua@vip.sina.com
Jing Liu, MD, 86 010 88326666, liujing0245@bjmu.edu.cn
About this study
Official title: Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia Patients Undergoing HSCT
Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly causes of transplant failure. We reported previously that patients with relapse or refractory AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastic syndrome. It was reported that the combination of decitabine, with busulfan and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a preparative regimen for allo-HSCT in recurrent and refractory AL patients.
Read the detailed description
Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.
BM(bone marrow) samples from patients were obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 years after transplantation.
- Being tested
- Decitabine, mBU/CY and ATG, mBU/CY
- Keywords
- recurrent acute leukemia, refractory acute leukemia, preconditioning regimen, allogeneic stem cell transplantation
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Decitabine 200mg.m-2.d-1 intravenously on days -12 and -11
mBU/CY and ATGDrug
Ara-C 4 g·m-2·d-1 intravenously on days -10 to -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Semustine (Me-CCNU, 250 mg·m-2) orally once on day -3 ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2
mBU/CYDrug
hydroxycarbamide (80 mg·kg-1) orally on day -10 Ara-C (2 g·m-2·d-1) on day -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Semustine (Me-CCNU, 250 mg·m-2) orally once on day -3
| Study group | Role | What they receive |
|---|---|---|
| Decitabine plus mBU/CY for HLA-mismatched HSCT | Experimental | Decitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT
Details:
The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2 Receives: Drug: Decitabine; Drug: mBU/CY and ATG |
| Decitabine plus mBU/CY for matched sibling transplant | Experimental | Decitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant.
Details:
In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3. Receives: Drug: Decitabine; Drug: mBU/CY |
What is being measured
The primary outcome is the main question the study is designed to answer.
1 year cumulative incidence of relapse
The cumulative incidence of relapse at 1 year post allo-HSCT
Measured: 1 year post allo-HSCT
2 year cumulative incidence of relapse
The cumulative incidence of relapse at 2 years post allo-HSCT
Measured: 2 years post allo-HSCT
Secondary outcomes (8)
Non-relapse mortality
The cumulative incidence of non-relapse mortality at 1 year post allo-HSCT
Measured: 1 year post allo-HSCT
1 year overall survival
The overall survival at 1 year post allo-HSCT
Measured: 1 year post allo-HSCT
5 years overall survival
The overall survival at 5 years post allo-HSCT
Measured: 5 years post allo-HSCT] 1 year leukemia free survival
1 year leukemia free survival
The leukemia free survival at 1 years post allo-HSCT
Measured: 1 year post allo-HSCT
5 years leukemia free survival
The leukemia free survival at 5 years post allo-HSCT
Measured: 5 years post allo-HSCT
engraftment
The total neutrophil and platelet engraftment rate
Measured: 100 days post allo-HSCT
Acute graft versus host disease
The cumulative incidence of grade II-IV acute graft versus host disease
Measured: 100 days post allo-HSCT
Chronic graft versus host disease
The cumulative incidence of intermediate to severe chronic graft versus host disease
Measured: 1 years post allo-HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2019
- Study start1 Dec 2018
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stem Cell Transplant ComplicationsStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.BM samples from patients would be obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 year after transplantation.
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiaojun Huang,MD, Peking University People's Hospital
- Investigators
- Xiao-Jun Huang, Study chair, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03799224
- Sponsor's protocol ID
- decitabine pre-HSCT for R/R AL
- Status last verified
- May 2019
- First submitted
- 8 Jan 2019
- Last updated
- 29 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decitabine Plus mBU/CY Preconditioning for Relapse/Refractory Acute Leukemia Patients Undergoing HSCT
- ClinicalTrials.gov ID
- NCT03799224
- Acronym / sponsor ID
- decitabine pre-HSCT for R/R AL
- Keywords
- recurrent acute leukemia, refractory acute leukemia, preconditioning regimen, allogeneic stem cell transplantation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 10 Jan 2019 (actual)
- 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 haematopoietic stem cell transplantation (allo-HSCT) remains one of the currently available curative therapies for acute leukemia (AL). Leukemia relapse is one of the mainly causes of transplant failure. We reported previously that patients with relapse or refractory AL were at very high risk of relapse post allo-HSCT, with cumulative relapse rate of 50-80%. Decitabine has been demonstrated efficacy in the treatment of patients with recurrent or refractory leukemia and myelodysplastic syndrome. It was reported that the combination of decitabine, with busulfan and cyclophosphamide as a preparative regimen for allo-HSCT using HLA-matching donors was safe and effective. In this prospective, single-arm clinical trial, we aimed to examine the efficacy of combining decitabine with modified busulfan and cyclophosphamide (mBU/CY) as a preparative regimen for allo-HSCT in recurrent and refractory AL patients.
Detailed description
Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG (thymoglobulin; Sang Stat, France) consisting of cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg·m-2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.
BM(bone marrow) samples from patients were obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 years after transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients enrolled in this study would receive decitabine 200mg·m-2·d-1 on day -12 and -11 pre-HSCT. The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was modified BU/CY plus ATG. In matched sibling transplantations, patients received hydroxycarbamide (80 mg·kg-1) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, but otherwise an identical regimen to the HLA-mismatched patients without ATG.BM samples from patients would be obtained to assess leukemia status after HSCT. The time points that we monitored BM samples included at time of allo-HSCT; 1 month, 2 months, 3 months, 4.5 months, 6 months, 9 months, and 12 months after allo-HSCT; and every 6 months thereafter to the defined endpoints or for at least until 5 year after transplantation.
| Arm | Type | Receives |
|---|---|---|
| Decitabine plus mBU/CY for HLA-mismatched HSCT | Experimental | Drug: Decitabine, Drug: mBU/CY and ATGDecitabine plus mBU/CY as precondition regimen for recurrent and refractory acute leukemia at the time of HLA-mismatched HSCT Details: The conditioning therapy for human leukocyte antigen (HLA)-mismatched HSCT patients was decitabine plus modified BU/CY and ATG,consisting of decitabine 100mg·m-2·d-1 q12h on days-12 and -11,cytarabine (Ara-C 4 g·m-2·d-1) intravenously on days -10 to -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3, and ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2 |
| Decitabine plus mBU/CY for matched sibling transplant | Experimental | Drug: Decitabine, Drug: mBU/CYDecitabine plus mBU/CY as precondition regimen for High Risk Acute Leukemia With MRD (minimal residual disease) at the time of matched sibling transplant. Details: In matched sibling transplantations, patients received decitabine 100mg·m-2·d-1 q12h on days-12 and -11,hydroxycarbamide (80 mg/kg) orally on day -10 and a lower dose of Ara-C (2 g·m-2·d-1) on day -9, busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, cyclophosphamide (CY 1.8 g·m-2·d-1), intravenously on days -5 to -4, semustine (Me-CCNU, 250 mg/m2), orally once on day -3. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- patients with relapsed acute leukemia
- patients with acute leukemia in the third（or more）complete remission (CR3) status
Key exclusion criteria (2 listed)
- pregnancy women
- uncontrolled severe infection
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 |
|---|---|---|
| DecitabineDecitabine 200mg.m-2.d-1 intravenously on days -12 and -11 | Drug | Decitabine plus mBU/CY for HLA-mismatched HSCT, Decitabine plus mBU/CY for matched sibling transplant |
| mBU/CY and ATGAra-C 4 g·m-2·d-1 intravenously on days -10 to -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Semustine (Me-CCNU, 250 mg·m-2) orally once on day -3 ATG (2.5 mg·kg-1·d-1) intravenously on days -5 to -2 | Drug | Decitabine plus mBU/CY for HLA-mismatched HSCT |
| mBU/CYhydroxycarbamide (80 mg·kg-1) orally on day -10 Ara-C (2 g·m-2·d-1) on day -9 Busulfan (BU 3.2 mg·kg-1·d-1) intravenously on days -8 to -6, Cyclophosphamide (CY 1.8 g·m-2·d-1) intravenously on days -5 to -4 Semustine (Me-CCNU, 250 mg·m-2) orally once on day -3 | Drug | Decitabine plus mBU/CY for matched sibling transplant |
Primary outcome
1 year cumulative incidence of relapse
Time frame: 1 year post allo-HSCT
The cumulative incidence of relapse at 1 year post allo-HSCT
2 year cumulative incidence of relapse
Time frame: 2 years post allo-HSCT
The cumulative incidence of relapse at 2 years post allo-HSCT
8 secondary outcomes
Non-relapse mortality
Time frame: 1 year post allo-HSCT
1 year overall survival
Time frame: 1 year post allo-HSCT
5 years overall survival
Time frame: 5 years post allo-HSCT] 1 year leukemia free survival
1 year leukemia free survival
Time frame: 1 year post allo-HSCT
5 years leukemia free survival
Time frame: 5 years post allo-HSCT
engraftment
Time frame: 100 days post allo-HSCT
Acute graft versus host disease
Time frame: 100 days post allo-HSCT
Chronic graft versus host disease
Time frame: 1 years post allo-HSCT
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2019.
- Individual participant dataSharing planned: No
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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.
Xiao-Jun Huang study chair
Peking University People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Decitabine, mBU/CY and ATG and mBU/CY in people with Stem Cell Transplant Complications and Relapse Leukemia, run by Peking University People's Hospital at 1 site in China.
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 2 inclusion and 2 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 29 May 2019. 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 China. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Xiao-Jun Huang (+86 010 88326666, yanchenhua@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1 year cumulative incidence of relapse (time frame: 1 year post allo-HSCT). The study lists 2 primary outcomes in all. 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 29 May 2019.