Clinical trial NCT03236220: Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2017-08-01
Enrollment: 35
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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%)

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

Primary outcomes:
measure: Incidence of poor graft function and prolonged isolated thrombocytopenia
timeFrame: Participants will be followed for 2 months post-HSCT.
Secondary outcomes:
measure: Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC.
timeFrame: From 14 days pre-HSCT to 2 months post-HSCT.
measure: Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment.
timeFrame: Participants will be followed for 100 days post-HSCT.
measure: Incidence of GVHD
timeFrame: Participants will be followed for 100 days post-HSCT.
measure: Incidence of relapse
timeFrame: Participants will be followed for 1 year post-HSCT.
measure: Incidence of viral infection
timeFrame: Participants will be followed for 100 days post-HSCT.
measure: Non-relapse mortality
timeFrame: Participants will be followed for 1 year post-HSCT.
measure: Progression-free survival
timeFrame: Participants will be followed for 1 year post-HSCT.
measure: Overall survival
timeFrame: Participants will be followed for 1 year post-HSCT.
Other outcomes:
Locations:
city: Beijng
country: China
facility: Peking University People's Hospital
Study officials:
affiliation: Peking University People's Hospital
name: Xiao-Jun Huang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.