Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation

NCT03236220 | Completed Phase 2 DMC

• 1 other identifier: 2015PHB220
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Haploidentical Hematopoietic Stem Cell Transplantation

Keywords

haploidentical hematopoietic stem cell transplantation; poor graft function; prolonged isolated thrombocytopenia; bone marrow endothelial cells; N-acetyl-L-cysteine; Acute leukemia

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  Participants will be followed for 100 days post-HSCT.

• Incidence of GVHD

  Participants will be followed for 100 days post-HSCT.

• Incidence of relapse

  Participants will be followed for 1 year post-HSCT.

• Incidence of viral infection

  Participants will be followed for 100 days post-HSCT.

Study Arms (1)

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.

Drug: N-acetyl-L-cysteine

Interventions

N-acetyl-L-cysteine DRUG

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.

Also known as: NAC

N-acetyl-L-cysteine group

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 patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation；

You may not qualify if:

• Bronchial asthma;
• Allergic to N-acetyl-L-cystein

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People's Hospital

Beijng, China

Location

Related Publications (1)

• 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.

  PMID: 31015207 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 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: July 23, 2017
• First Posted: August 1, 2017
• Study Start: August 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 17, 2020

Record last verified: 2020-09

Locations

CN (1)