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

Haploidentical Hematopoietic Stem Cell Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03236220
• Other study ID #: 2015PHB220
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2017
• Est. completion date: December 1, 2018

Study information

• Verified date: September 2020
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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%)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 1, 2018
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Haploidentical Hematopoietic Stem Cell Transplantation
• Thrombocytopenia

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijng

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	From 14 days pre-HSCT to 2 months post-HSCT.
Secondary	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.	Participants will be followed for 100 days post-HSCT.
Secondary	Incidence of GVHD	Number of participants with I-IV aGVHD will be observed for 100 days post-HSCT.	Participants will be followed for 100 days post-HSCT.
Secondary	Incidence of relapse	Number of participants with morphologic relapse will be calculated at one year post-HSCT.	Participants will be followed for 1 year post-HSCT.
Secondary	Incidence of viral infection	Number of participants with viral infection(CMV,EBV,et al) will be observed for 100 days post-HSCT.	Participants will be followed for 100 days post-HSCT.
Secondary	Non-relapse mortality	Number of participants with non-relapse mortality will be observed for 1 year post-HSCT.	Participants will be followed for 1 year post-HSCT.
Secondary	Progression-free survival	Number of participants survived with progression-free will be observed for 1 year post-HSCT.	Participants will be followed for 1 year post-HSCT.
Secondary	Overall survival	Number of participants survived for 1 year post-HSCT will be calculated.	Participants will be followed for 1 year post-HSCT.