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

NCT ID: NCT03236220

Last Updated: 2020-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2018-12-01

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.

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

1. Severe toxicity occurrence

2. Cumulative incidence of relapse increased) (≥ 30%)

3. Cumulative incidence of mortality increased (≥ 30%)

4. Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)

Conditions

Haploidentical Hematopoietic Stem Cell Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

N-acetyl-L-cysteine group

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.

Group Type: EXPERIMENTAL

N-acetyl-L-cysteine

Intervention Type: 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.

Interventions

N-acetyl-L-cysteine

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.

Intervention Type: DRUG

Other Intervention Names

NAC

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

1. Bronchial asthma;

2. Allergic to N-acetyl-L-cystein

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Huang,MD

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-Jun Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Locations

Peking University People's Hospital

Beijng, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 31015207 (View on PubMed)

Other Identifiers

2015PHB220

Identifier Type: -

Identifier Source: org_study_id