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

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ClinicalTrials.gov Identifier: NCT03236220
Recruitment Status : Recruiting
First Posted : August 1, 2017
Last Update Posted : August 9, 2017
Sponsor:
Information provided by (Responsible Party):
Xiaojun Huang, Peking University People's Hospital

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.

Condition or disease Intervention/treatment Phase
Haploidentical Hematopoietic Stem Cell Transplantation Drug: N-acetyl-L-cysteine Phase 2

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%)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Prevention
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
Actual Study Start Date : August 1, 2017
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: 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.
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.
Other Name: NAC




Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03236220


Contacts
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Contact: Xiao-Jun Huang, MD 86-10-88326006 xjhrm@medmail.com.cn

Locations
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China
Peking University People's Hospital Recruiting
Beijng, China
Contact: Yuan Kong, MD,PhD    86-10-88324670    successky@163.com   
Sponsors and Collaborators
Peking University People's Hospital
Investigators
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Principal Investigator: Xiao-Jun Huang, MD Peking University People's Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Xiaojun Huang, Director, Peking University People's Hospital
ClinicalTrials.gov Identifier: NCT03236220     History of Changes
Other Study ID Numbers: 2015PHB220
First Posted: August 1, 2017    Key Record Dates
Last Update Posted: August 9, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xiaojun Huang, Peking University People's Hospital:
haploidentical hematopoietic stem cell transplantation
poor graft function
prolonged isolated thrombocytopenia
bone marrow endothelial cells
N-acetyl-L-cysteine
Acute leukemia

Additional relevant MeSH terms:
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Thrombocytopenia
Blood Platelet Disorders
Hematologic Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes