Risk Stratification-directed NAC for Prevention of Poor Hematopoietic Reconstitution

NCT03967665 | Unknown Phase 3

• 1 other identifier: NAC prevention of PGF and PT
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Stem Cell Transplant Complications

Keywords

N-acetyl-L-cysteine; Poor hematopoietic reconstitution; Unmanipulated Haploidentical stem cell Transplantation

Outcome Measures

Primary Outcomes (1)

• The incidence of poor hematopoietic reconstitution at 2 months post-HSCT

  The incidence of poor hematopoietic reconstitutio at 2 months post-HSCT

  2 months post-HSCT

Secondary Outcomes (10)

• Cumulative incidences of relapse at one year post-HSCT

  1 year after transplantation

• Cumulative incidences of acute graft-versus-host disease for 100 days post-HSCT

  100 days after transplantation

• Non-relapse mortality during 1 year post-HSCT

  1 year after transplantation

• Overall survival during 1 year post-HSCT

  1 year after transplantation

• Disease free survival during 1 year post-HSCT

  1 year after transplantation

Study Arms (2)

Treatment arm

EXPERIMENTAL

NAC 400 mg three times per day from -14D pre-HSCT to +2 months

Drug: N-acetyl-L-cysteine

Control arm

NO INTERVENTION

No-NAC concurrent control according to a 2:1 schedule.

Interventions

N-acetyl-L-cysteine DRUG

NAC 400 mg three times per day from -14D pre-HSCT to +2 months post-HSCT

Also known as: NAC

Treatment arm

Eligibility Criteria

• Age: 15 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People's Hospital

Beijing, 100044, China

Location

Related Publications (1)

• 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.

  PMID: 35473809 DERIVED

MeSH Terms

Interventions

Acetylcysteine

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Xiao-Jun Huang, MD

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Supervisor of Hematology,Peking University People's Hospital

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: May 30, 2019
• Study Start: October 1, 2018
• Primary Completion: September 5, 2021
• Study Completion: October 1, 2024
• Last Updated: September 14, 2021

Record last verified: 2021-09

Locations

CN (1)