Stem Cell Transplant ComplicationsPhase 3NCT03967665
Risk Stratification-directed NAC for Prevention of Poor Hematopoietic Reconstitution
A Phase 3 study testing N-acetyl-L-cysteine in people with Stem Cell Transplant Complications, run by Peking University People's Hospital at 1 site in China.
Trial summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of malignant hematopoietic diseases. However, poor hematopoietic reconstitution including poor graft function (PGF) and prolonged isolated thrombocytopenia (PT), remains a life-threatening complication after allo-HSCT. Read more about this study
- Who is it for?
- Ages 15 to 60 years
- Conditions the study is for
- Stem Cell Transplant Complications
- What is being tested?
- N-acetyl-L-cysteine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2018to 1 Oct 2024
- Phase
- Phase 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 15 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Acute leukemia in the first complete remission (CR1) at time of haplo- transplant.
- Age ≥ 15 years.
- Contraception: Female patients of childbearing potential must use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and until the end of treatment visit.
- Must provide written informed consent and agree to comply with the trial protocol.
Who cannot join
- History or presence of allergy to NAC.
- History or presence of clinically concerning Bronchial asthma.
- Non-CR1 leukemia at time of transplant.
- Patients undergoing transplant from donors other than haploidentical relatives.
- Patients who have previously participated in a clinical trial of NAC.
- If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Risk Stratification-directed N-acetyl-L-cysteine for Prevention of Poor Hematopoietic Reconstitution After Unmanipulated Haploidentical Stem Cell Transplantation--an Open-label, Randomized, Controlled, Clinical Trial
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of malignant hematopoietic diseases. However, poor hematopoietic reconstitution including poor graft function (PGF) and prolonged isolated thrombocytopenia (PT), remains a life-threatening complication after allo-HSCT. Especially with the increasing use of haploidentical allo-HSCT (haplo-HSCT) in the past ten years, PGF and PT have become growing obstacles contributing to high morbidity and mortality after allo-HSCT. Due to the limited mechanism studies, the clinical management of PGF and PT is challenging.
Recent prospective case-control studies reported that the reduced and dysfunctional bone marrow (BM) endothelial cells (ECs) after allo-HSCT are involved in the pathogenesis of PGF and PT. Moreover, in vitro treatment with N-acetyl-L-cysteine (NAC) could enhance the defective hematopoietic stem cell (HSC) function through repairing the dysfunctional BM ECs of PGF and PT patients. The investigators performed a small-scale pilot cohort study and saw encouraging clinical results that oral administration with NAC could partially repair the dysfunctional BM ECs and improve megakaryocytopoiesis in PT patients, which suggests that NAC is a promising drug in PT patients after allo-HSCT. In addition, prior prospective trial of the investigators suggests that BM ECs<0.1% pre-HSCT is the risk factor for occurrence of the PGF and PT two months following allo-HSCT. Previous single-arm clinical cohort studies of the investigators showed that prophylactic use of NAC before allo-HSCT reduced the incidence of poor hematopoietic reconstitution after allo-HSCT in patients with ECs <0.1% pre-HSCT.
Therefore, the investigators designed the study with acute leukemia patients who will be scheduled to receive haplo-HSCT. The patients who are in the first complete remission at time of haplo-transplant will be enrolled in the study. Exclusive criteria are bronchila asthma and NAC allergy. The enrolled patients were risk-stratified into BM ECs≥0.1% group (low-risk group) and BM ECs<0.1% group (high-risk group). Patients in high-risk group (ECs<0.1%) will be randomized to 1 of 2 arms: (a) NAC 400 mg three times per day from 14 days pre-HSCT to 2 months post-HSCT, (b) No-NAC concurrent control according to a 2:1 schedule. The aim of the trail is to assess the effects of NAC for prevention of poor hematopoietic reconstitution in patients with acute leukemia undergoing haplo-HSCT.
Read the detailed description
This study is designed as a phase III, open-label, randomized study assessing the safety and efficacy of NAC (400 mg, orally, three times daily) versus no-NAC control for prevention of poor hematopoietic reconstitution in patients with acute leukemia undergoing haploidentical HSCT in a 2:1 ratio. The study will consist of three phases: a pre-randomization phase, a treatment phase, and an observational follow-up phase.
The screening period: Patients will be screened during a 1 week screening period prior to entering the trial to allow for the collection of BM samples to evaluate the quantity and function of BM ECs at 21-14 days before HSCT. The enrolled patients were risk-stratified into BM ECs≥0.1% group (low-risk group) and BM ECs<0.1% group (high-risk group). Approximately 126 patients with BM EC <0.1% at day-14 pre-HSCT (84 patients in NAC treatment arm and 42 patients in control arm) will be randomized in a 2:1 ratio to 1 of 2 arms: (a) NAC 400 mg three times per day, (b) No-NAC concurrent control.
The treatment phase: Study medication will be administered orally, 400 mg three times daily from -14 days pre-HSCT to +2 months post-HSCT. All patients should continue their pre study dose of NAC throughout trial participation. Following randomization, patients will have 3 hospitalized or at-clinic trial visits at day 0 before-HSCT and 1, 2 months post-HSCT to evaluate efficacy, safety, tolerability and compliance with study medication. Patients will be contacted by trial site staff on a monthly basis between visits beginning with day 0.
The observational follow-up phase: Upon completion of the trial participation phase all eligible patients will enter an open label follow-up phase. Clinic visits will occur every 3 months (± 1 week).
Patients will have a pretreatment bone marrow aspiration conducted and have a follow up bone marrow aspiration conducted at day0 before-HSCT and 1, and 2 months post-HSCT. All patients who complete or discontinue from the trial, for any reason, will have a follow up visit, 4 weeks after their last dose of study medication. The primary outcome is the incidence of PGF and PT at 2 months after HSCT, as well as the safety. Secondary endpoints included cumulative incidences of relapse (CIR), acute graft-versus-host disease (aGVHD), non-relapse mortality (NRM), overall survival (OS), disease free survival (DFS), the related laboratory evaluation of ECs and HSC in BM microenvironment, etc.
- Conditions
- Stem Cell Transplant Complications
- Being tested
- N-acetyl-L-cysteine
- Keywords
- N-acetyl-L-cysteine, Poor hematopoietic reconstitution, Unmanipulated Haploidentical stem cell Transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetyl-L-cysteineDrug
Also called NAC
NAC 400 mg three times per day from -14D pre-HSCT to +2 months post-HSCT
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | NAC 400 mg three times per day from -14D pre-HSCT to +2 months Receives: Drug: N-acetyl-L-cysteine |
| Control arm | No intervention | No-NAC concurrent control according to a 2:1 schedule. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of poor hematopoietic reconstitution at 2 months post-HSCT
The incidence of poor hematopoietic reconstitutio at 2 months post-HSCT
Measured: 2 months post-HSCT
Secondary outcomes (10)
Cumulative incidences of relapse at one year post-HSCT
Cumulative incidences of relapse at one year post-HSCT.
Measured: 1 year after transplantation
Cumulative incidences of acute graft-versus-host disease for 100 days post-HSCT
Cumulative incidences of acute graft-versus-host disease for 100 days post-HSCT
Measured: 100 days after transplantation
Non-relapse mortality during 1 year post-HSCT
Non-relapse mortality during 1 year post-HSCT
Measured: 1 year after transplantation
Overall survival during 1 year post-HSCT
Overall survival during 1 year post-HSCT
Measured: 1 year after transplantation
Disease free survival during 1 year post-HSCT
Disease free survival during 1 year post-HSCT
Measured: 1 year after transplantation
Number of participants with treatment-related adverse events during oral administration of NAC.
Number of participants with treatment-related adverse events during oral administration of NAC.
Measured: 14 days pre-HSCT to 2 months post-HSCT.
Effect of NAC on ECs percentage at 0 day pre-HSCT, 1 month, 2 months post-HSCT
ECs percentages at 0 day pre-HSCT, 1 month, 2 months post-HSCT
Measured: 0 day pre-HSCT, 1 month, 2 months post-HSCT
Effect of NAC on HSCs percentagesat 0 day pre-HSCT, 1 month, 2 months post-HSCT
HSCs percentages at 0 day pre-HSCT, 1 month, 2 months post-HSCT
Measured: 0 day pre-HSCT, 1 month, 2 months post-HSCT
Effect of NAC on MKs numbers at 0 day pre-HSCT, 1 month, 2 months post-HSCT
MKs numbers at 0 day pre-HSCT, 1 month, 2 months post-HSCT
Measured: 0 day pre-HSCT, 1 month, 2 months post-HSCT
Incidence of viral infection until 100 days post-HSCT.
Incidence of viral infection until 100 days post-HSCT.
Measured: 100 days post-HSCT.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2019
- Study start1 Oct 2018
- Primary completion5 Sep 2021
- Study completion1 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stem Cell Transplant ComplicationsStudies of the same condition, open and under way.
- More trials run by Peking University People's 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiao-Jun Huang, Peking University People's Hospital
- Investigators
- Xiao-Jun Huang, MD, Principal investigator, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03967665
- Sponsor's protocol ID
- NAC prevention of PGF and PT
- Status last verified
- Sep 2021
- First submitted
- 3 Apr 2019
- Last updated
- 14 Sep 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wang Y, Kong Y, Zhao HY, Zhang YY, Wang YZ, Xu LP, Zhang XH, Liu KY, Huang XJ. Prophylactic NAC promoted hematopoietic reconstitution by improving endothelial cells after haploidentical HSCT: a phase 3, open-label randomized trial. BMC Med. 2022 Apr 27;20(1):140. doi: 10.1186/s12916-022-02338-9.
PubMed 35473809
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk Stratification-directed N-acetyl-L-cysteine for Prevention of Poor Hematopoietic Reconstitution After Unmanipulated Haploidentical Stem Cell Transplantation--an Open-label, Randomized, Controlled, Clinical Trial
- ClinicalTrials.gov ID
- NCT03967665
- Acronym / sponsor ID
- NAC prevention of PGF and PT
- Conditions
- Stem Cell Transplant Complications
- Keywords
- N-acetyl-L-cysteine, Poor hematopoietic reconstitution, Unmanipulated Haploidentical stem cell Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 5 Sep 2021 (actual)
- Study completion
- 1 Oct 2024 (estimated)
- First posted
- 30 May 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 hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of malignant hematopoietic diseases. However, poor hematopoietic reconstitution including poor graft function (PGF) and prolonged isolated thrombocytopenia (PT), remains a life-threatening complication after allo-HSCT. Especially with the increasing use of haploidentical allo-HSCT (haplo-HSCT) in the past ten years, PGF and PT have become growing obstacles contributing to high morbidity and mortality after allo-HSCT. Due to the limited mechanism studies, the clinical management of PGF and PT is challenging.
Recent prospective case-control studies reported that the reduced and dysfunctional bone marrow (BM) endothelial cells (ECs) after allo-HSCT are involved in the pathogenesis of PGF and PT. Moreover, in vitro treatment with N-acetyl-L-cysteine (NAC) could enhance the defective hematopoietic stem cell (HSC) function through repairing the dysfunctional BM ECs of PGF and PT patients. The investigators performed a small-scale pilot cohort study and saw encouraging clinical results that oral administration with NAC could partially repair the dysfunctional BM ECs and improve megakaryocytopoiesis in PT patients, which suggests that NAC is a promising drug in PT patients after allo-HSCT. In addition, prior prospective trial of the investigators suggests that BM ECs<0.1% pre-HSCT is the risk factor for occurrence of the PGF and PT two months following allo-HSCT. Previous single-arm clinical cohort studies of the investigators showed that prophylactic use of NAC before allo-HSCT reduced the incidence of poor hematopoietic reconstitution after allo-HSCT in patients with ECs <0.1% pre-HSCT.
Therefore, the investigators designed the study with acute leukemia patients who will be scheduled to receive haplo-HSCT. The patients who are in the first complete remission at time of haplo-transplant will be enrolled in the study. Exclusive criteria are bronchila asthma and NAC allergy. The enrolled patients were risk-stratified into BM ECs≥0.1% group (low-risk group) and BM ECs<0.1% group (high-risk group). Patients in high-risk group (ECs<0.1%) will be randomized to 1 of 2 arms: (a) NAC 400 mg three times per day from 14 days pre-HSCT to 2 months post-HSCT, (b) No-NAC concurrent control according to a 2:1 schedule. The aim of the trail is to assess the effects of NAC for prevention of poor hematopoietic reconstitution in patients with acute leukemia undergoing haplo-HSCT.
Detailed description
This study is designed as a phase III, open-label, randomized study assessing the safety and efficacy of NAC (400 mg, orally, three times daily) versus no-NAC control for prevention of poor hematopoietic reconstitution in patients with acute leukemia undergoing haploidentical HSCT in a 2:1 ratio. The study will consist of three phases: a pre-randomization phase, a treatment phase, and an observational follow-up phase.
The screening period: Patients will be screened during a 1 week screening period prior to entering the trial to allow for the collection of BM samples to evaluate the quantity and function of BM ECs at 21-14 days before HSCT. The enrolled patients were risk-stratified into BM ECs≥0.1% group (low-risk group) and BM ECs<0.1% group (high-risk group). Approximately 126 patients with BM EC <0.1% at day-14 pre-HSCT (84 patients in NAC treatment arm and 42 patients in control arm) will be randomized in a 2:1 ratio to 1 of 2 arms: (a) NAC 400 mg three times per day, (b) No-NAC concurrent control.
The treatment phase: Study medication will be administered orally, 400 mg three times daily from -14 days pre-HSCT to +2 months post-HSCT. All patients should continue their pre study dose of NAC throughout trial participation. Following randomization, patients will have 3 hospitalized or at-clinic trial visits at day 0 before-HSCT and 1, 2 months post-HSCT to evaluate efficacy, safety, tolerability and compliance with study medication. Patients will be contacted by trial site staff on a monthly basis between visits beginning with day 0.
The observational follow-up phase: Upon completion of the trial participation phase all eligible patients will enter an open label follow-up phase. Clinic visits will occur every 3 months (± 1 week).
Patients will have a pretreatment bone marrow aspiration conducted and have a follow up bone marrow aspiration conducted at day0 before-HSCT and 1, and 2 months post-HSCT. All patients who complete or discontinue from the trial, for any reason, will have a follow up visit, 4 weeks after their last dose of study medication. The primary outcome is the incidence of PGF and PT at 2 months after HSCT, as well as the safety. Secondary endpoints included cumulative incidences of relapse (CIR), acute graft-versus-host disease (aGVHD), non-relapse mortality (NRM), overall survival (OS), disease free survival (DFS), the related laboratory evaluation of ECs and HSC in BM microenvironment, etc.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: N-acetyl-L-cysteineNAC 400 mg three times per day from -14D pre-HSCT to +2 months |
| Control arm | No intervention | –No-NAC concurrent control according to a 2:1 schedule. |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Acute leukemia in the first complete remission (CR1) at time of haplo- transplant.
- Age ≥ 15 years.
- Contraception: Female patients of childbearing potential must use ≥ 1 effective (≤ 1% failure rate) method of contraception during the trial and until the end of treatment visit.
- Must provide written informed consent and agree to comply with the trial protocol.
Key exclusion criteria (6 listed)
- History or presence of allergy to NAC.
- History or presence of clinically concerning Bronchial asthma.
- Non-CR1 leukemia at time of transplant.
- Patients undergoing transplant from donors other than haploidentical relatives.
- Patients who have previously participated in a clinical trial of NAC.
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 |
|---|---|---|
| N-acetyl-L-cysteineAlso: NACNAC 400 mg three times per day from -14D pre-HSCT to +2 months post-HSCT | Drug | Treatment arm |
Primary outcome
The incidence of poor hematopoietic reconstitution at 2 months post-HSCT
Time frame: 2 months post-HSCT
The incidence of poor hematopoietic reconstitutio at 2 months post-HSCT
10 secondary outcomes
Cumulative incidences of relapse at one year post-HSCT
Time frame: 1 year after transplantation
Cumulative incidences of acute graft-versus-host disease for 100 days post-HSCT
Time frame: 100 days after transplantation
Non-relapse mortality during 1 year post-HSCT
Time frame: 1 year after transplantation
Overall survival during 1 year post-HSCT
Time frame: 1 year after transplantation
Disease free survival during 1 year post-HSCT
Time frame: 1 year after transplantation
Number of participants with treatment-related adverse events during oral administration of NAC.
Time frame: 14 days pre-HSCT to 2 months post-HSCT.
Effect of NAC on ECs percentage at 0 day pre-HSCT, 1 month, 2 months post-HSCT
Time frame: 0 day pre-HSCT, 1 month, 2 months post-HSCT
Effect of NAC on HSCs percentagesat 0 day pre-HSCT, 1 month, 2 months post-HSCT
Time frame: 0 day pre-HSCT, 1 month, 2 months post-HSCT
Effect of NAC on MKs numbers at 0 day pre-HSCT, 1 month, 2 months post-HSCT
Time frame: 0 day pre-HSCT, 1 month, 2 months post-HSCT
Incidence of viral infection until 100 days post-HSCT.
Time frame: 100 days post-HSCT.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2021.
- Derived from this study: PubMed 35473809Wang Y, Kong Y, Zhao HY, Zhang YY, Wang YZ, Xu LP, Zhang XH, Liu KY, Huang XJ. Prophylactic NAC promoted hematopoietic reconstitution by improving endothelial cells after haploidentical HSCT: a phase 3, open-label randomized trial. BMC Med. 2022 Apr 27;20(1):140. doi: 10.1186/s12916-022-02338-9.
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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, MD principal investigator
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 3 study testing N-acetyl-L-cysteine in people with Stem Cell Transplant Complications, 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 4 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: status not confirmed, as of the sponsor's last update on 14 Sep 2021. 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 phase mean?
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?
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?
The incidence of poor hematopoietic reconstitution at 2 months post-HSCT (time frame: 2 months post-HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03967665, which also lists 1 linked publication.
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 14 Sep 2021.