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NCT Number: NCT03236220

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

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.

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Key information

Conditions

Haploidentical Hematopoietic Stem Cell Transplantation

Age range

15 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Peking University People's Hospital

Beijng, China

About this study

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

  • Severe toxicity occurrence
  • Cumulative incidence of relapse increased) (≥ 30%)
  • Cumulative incidence of mortality increased (≥ 30%)
  • Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

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

Treatment and study plan

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.

Other names: NAC

Primary outcomes

  1. Incidence of poor graft function and prolonged isolated thrombocytopenia

    Time frame: Participants will be followed for 2 months post-HSCT.

    Number of participants with poor graft function and prolonged isolated thrombocytopenia will be calculated at 2-month post-HSCT.

Secondary outcomes

  1. Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC.

    Time frame: From 14 days pre-HSCT to 2 months post-HSCT.

    Participants will be closely observed for NAC-related toxicities during the NAC administration until 2-month post-HSCT.

  2. Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment.

    Time frame: Participants will be followed for 100 days post-HSCT.

    Examine hematopoietic stem cells, megakaryocytes and the elements of bone

    marrow microenvironment by flow cytometry and bone marrow histological examination.

  3. Incidence of GVHD

    Time frame: Participants will be followed for 100 days post-HSCT.

    Number of participants with I-IV aGVHD will be observed for 100 days post-HSCT.

  4. Incidence of relapse

    Time frame: Participants will be followed for 1 year post-HSCT.

    Number of participants with morphologic relapse will be calculated at one year post-HSCT.

  5. Incidence of viral infection

    Time frame: Participants will be followed for 100 days post-HSCT.

    Number of participants with viral infection(CMV,EBV,et al) will be observed for 100 days post-HSCT.

  6. Non-relapse mortality

    Time frame: Participants will be followed for 1 year post-HSCT.

    Number of participants with non-relapse mortality will be observed for 1 year post-HSCT.

  7. Progression-free survival

    Time frame: Participants will be followed for 1 year post-HSCT.

    Number of participants survived with progression-free will be observed for 1 year post-HSCT.

  8. Overall survival

    Time frame: Participants will be followed for 1 year post-HSCT.

    Number of participants survived for 1 year post-HSCT will be calculated.

Sponsors and collaborators

Lead sponsor

Peking University People's Hospital

Other

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Aug 1, 2017
Registry last updated
Sep 17, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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