Haploidentical Hematopoietic Stem Cell TransplantationPhase 2NCT03236220
Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation
A Phase 2 study testing N-acetyl-L-cysteine in people with Haploidentical Hematopoietic Stem Cell Transplantation, run by Peking University People's Hospital at 1 site in China.
Trial summary
The aim of the study is to evaluate the efficacy of the prophylactic administration of N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and post-allotransplant on the occurrence of poor graft function (PGF) and prolonged isolated thrombocytopenia (PT) after haploidentical hematopoietic… Read more about this study
- Who is it for?
- Ages 15 to 60 years
- Conditions the study is for
- Haploidentical Hematopoietic Stem Cell Transplantation
- What is being tested?
- N-acetyl-L-cysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2017to 1 Dec 2018
- 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 15 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation；
Who cannot join
- Bronchial asthma;
- Allergic to N-acetyl-L-cystein
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of the Prophylactic Intervention of N-acetyl-L-cysteine (NAC) on the Incidence of Poor Graft Function and Prolonged Isolated Thrombocytopenia in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation
The aim of the study is to evaluate the efficacy of the prophylactic administration of N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and post-allotransplant on the occurrence of poor graft function (PGF) and prolonged isolated thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplantation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of malignant hematopoietic diseases. However, the delayed hematopoietic reconstitution, including PGF and PT, remain serious complication after allo-HSCT, and the effective therapeutic strategies are limited. In murine studies, endothelial cells have been identified as a key cellular component supporting hematopoietic stem cells in the bone marrow microenvironment. Our previous prospective nested case-control study suggested that the frequency of bone marrow endothelial cells was markedly reduced in patients with PGF or PT. Moreover, our recent study further identified reduced bone marrow endothelial cells (<0.1%) pre-allotransplant was associated with significant higher incidences of PGF or PT after allo-HSCT. In addition, NAC treatment in vitro could quantitatively and functionally improve bone marrow endothelial cells derived from the patients with PGF or PT. Therefore, bone marrow endothelial cells (<0.1%) pre-allotransplant can be used to identify patients with a higher incidence of PGF or PT to provide timely prophylactic intervention of NAC to prevent the occurrence of delayed hematopoietic reconstitution post-transplant. The study hypothesis: Prophylactic intervention of NAC pre- and post-allotransplant could reduce the incidence of PGF and PT in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.
Read the detailed description
Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive NAC (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity. The effect of NAC on hematopoietic stem cells, megakaryocytes, immunologic subsets, and the elements of bone marrow microenvironment will be monitored pre- and post-allotransplant.
Drug：N-acetyl-L-cysteine (NAC) is orally administrated at dosages of 400mg 3 times per day. NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity.
Participant：Acute leukemia patients with CR, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation.
Eligibility Ages Eligible for Study: 15-60 Years Genders Eligible for Study: Both Accepts The trial will be terminated in following situation
- Severe toxicity occurrence
- Cumulative incidence of relapse increased) (≥ 30%)
- Cumulative incidence of mortality increased (≥ 30%)
- Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)
- Being tested
- N-acetyl-L-cysteine
- Keywords
- haploidentical hematopoietic stem cell transplantation, poor graft function, prolonged isolated thrombocytopenia, bone marrow endothelial cells, N-acetyl-L-cysteine, Acute leukemia
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
Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine (NAC) (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| N-acetyl-L-cysteine group | Experimental | Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine. Receives: Drug: N-acetyl-L-cysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of poor graft function and prolonged isolated thrombocytopenia
Number of participants with poor graft function and prolonged isolated thrombocytopenia will be calculated at 2-month post-HSCT.
Measured: Participants will be followed for 2 months post-HSCT.
Secondary outcomes (8)
Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC.
Participants will be closely observed for NAC-related toxicities during the NAC administration until 2-month post-HSCT.
Measured: From 14 days pre-HSCT to 2 months post-HSCT.
Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment.
Examine hematopoietic stem cells, megakaryocytes and the elements of bone
marrow microenvironment by flow cytometry and bone marrow histological examination.
Measured: Participants will be followed for 100 days post-HSCT.
Incidence of GVHD
Number of participants with I-IV aGVHD will be observed for 100 days post-HSCT.
Measured: Participants will be followed for 100 days post-HSCT.
Incidence of relapse
Number of participants with morphologic relapse will be calculated at one year post-HSCT.
Measured: Participants will be followed for 1 year post-HSCT.
Incidence of viral infection
Number of participants with viral infection(CMV,EBV,et al) will be observed for 100 days post-HSCT.
Measured: Participants will be followed for 100 days post-HSCT.
Non-relapse mortality
Number of participants with non-relapse mortality will be observed for 1 year post-HSCT.
Measured: Participants will be followed for 1 year post-HSCT.
Progression-free survival
Number of participants survived with progression-free will be observed for 1 year post-HSCT.
Measured: Participants will be followed for 1 year post-HSCT.
Overall survival
Number of participants survived for 1 year post-HSCT will be calculated.
Measured: Participants will be followed for 1 year post-HSCT.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2017
- Study start1 Aug 2017
- Primary completion1 Jul 2018
- Study completion1 Dec 2018
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 Haploidentical Hematopoietic Stem Cell TransplantationStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
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, MD, Principal investigator, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236220
- Sponsor's protocol ID
- 2015PHB220
- Status last verified
- Sep 2020
- First submitted
- 23 Jul 2017
- Last updated
- 17 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kong Y, Wang Y, Zhang YY, Shi MM, Mo XD, Sun YQ, Chang YJ, Xu LP, Zhang XH, Liu KY, Huang XJ. Prophylactic oral NAC reduced poor hematopoietic reconstitution by improving endothelial cells after haploidentical transplantation. Blood Adv. 2019 Apr 23;3(8):1303-1317. doi: 10.1182/bloodadvances.2018029454.
PubMed 31015207
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of the Prophylactic Intervention of N-acetyl-L-cysteine (NAC) on the Incidence of Poor Graft Function and Prolonged Isolated Thrombocytopenia in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03236220
- Acronym / sponsor ID
- 2015PHB220
- Keywords
- haploidentical hematopoietic stem cell transplantation, poor graft function, prolonged isolated thrombocytopenia, bone marrow endothelial cells, N-acetyl-L-cysteine, Acute leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 1 Aug 2017 (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.
The aim of the study is to evaluate the efficacy of the prophylactic administration of N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and post-allotransplant on the occurrence of poor graft function (PGF) and prolonged isolated thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplantation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of malignant hematopoietic diseases. However, the delayed hematopoietic reconstitution, including PGF and PT, remain serious complication after allo-HSCT, and the effective therapeutic strategies are limited. In murine studies, endothelial cells have been identified as a key cellular component supporting hematopoietic stem cells in the bone marrow microenvironment. Our previous prospective nested case-control study suggested that the frequency of bone marrow endothelial cells was markedly reduced in patients with PGF or PT. Moreover, our recent study further identified reduced bone marrow endothelial cells (<0.1%) pre-allotransplant was associated with significant higher incidences of PGF or PT after allo-HSCT. In addition, NAC treatment in vitro could quantitatively and functionally improve bone marrow endothelial cells derived from the patients with PGF or PT. Therefore, bone marrow endothelial cells (<0.1%) pre-allotransplant can be used to identify patients with a higher incidence of PGF or PT to provide timely prophylactic intervention of NAC to prevent the occurrence of delayed hematopoietic reconstitution post-transplant. The study hypothesis: Prophylactic intervention of NAC pre- and post-allotransplant could reduce the incidence of PGF and PT in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.
Detailed description
Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive NAC (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity. The effect of NAC on hematopoietic stem cells, megakaryocytes, immunologic subsets, and the elements of bone marrow microenvironment will be monitored pre- and post-allotransplant.
Drug：N-acetyl-L-cysteine (NAC) is orally administrated at dosages of 400mg 3 times per day. NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity.
Participant：Acute leukemia patients with CR, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation.
Eligibility Ages Eligible for Study: 15-60 Years Genders Eligible for Study: Both Accepts The trial will be terminated in following situation
- Severe toxicity occurrence
- Cumulative incidence of relapse increased) (≥ 30%)
- Cumulative incidence of mortality increased (≥ 30%)
- Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N-acetyl-L-cysteine group | Experimental | Drug: N-acetyl-L-cysteineAcute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine. |
Who may qualify
- Ages
- 15 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation；
Key exclusion criteria (2 listed)
- Bronchial asthma;
- Allergic to N-acetyl-L-cystein
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: NACAcute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine (NAC) (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity. | Drug | N-acetyl-L-cysteine group |
Primary outcome
Incidence of poor graft function and prolonged isolated thrombocytopenia
Time frame: Participants will be followed for 2 months post-HSCT.
Number of participants with poor graft function and prolonged isolated thrombocytopenia will be calculated at 2-month post-HSCT.
8 secondary outcomes
Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC.
Time frame: From 14 days pre-HSCT to 2 months post-HSCT.
Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment.
Time frame: Participants will be followed for 100 days post-HSCT.
Incidence of GVHD
Time frame: Participants will be followed for 100 days post-HSCT.
Incidence of relapse
Time frame: Participants will be followed for 1 year post-HSCT.
Incidence of viral infection
Time frame: Participants will be followed for 100 days post-HSCT.
Non-relapse mortality
Time frame: Participants will be followed for 1 year post-HSCT.
Progression-free survival
Time frame: Participants will be followed for 1 year post-HSCT.
Overall survival
Time frame: Participants will be followed for 1 year post-HSCT.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Derived from this study: PubMed 31015207Kong Y, Wang Y, Zhang YY, Shi MM, Mo XD, Sun YQ, Chang YJ, Xu LP, Zhang XH, Liu KY, Huang XJ. Prophylactic oral NAC reduced poor hematopoietic reconstitution by improving endothelial cells after haploidentical transplantation. Blood Adv. 2019 Apr 23;3(8):1303-1317. doi: 10.1182/bloodadvances.2018029454.
- Individual participant dataSharing planned: Undecided
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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 2 study testing N-acetyl-L-cysteine in people with Haploidentical Hematopoietic Stem Cell Transplantation, 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 1 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: finished, as of the sponsor's last update on 17 Sep 2020. 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 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of poor graft function and prolonged isolated thrombocytopenia (time frame: Participants will be followed for 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 NCT03236220, 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 17 Sep 2020.