NAC for Hematopoietic Recovery in SAA

N-acetyl-L-cysteine for Promoting Hematopoietic Recovery in Patients With Severe Aplastic Anemia (SAA) After Haploidentical Transplantation -- a Prospective Single-arm Clinical Study

This is a prospective single-arm clinical study to evaluate the role of NAC among patients with severe aplastic anemia (SAA) can promote hematopoietic recovery after haploidentical transplantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: N Acetyl L Cysteine

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of severe aplastic anemia (SAA). However, poor hematopoietic reconstitution including poor graft function (PGF) and prolonged isolated thrombocytopenia (PT), remains a life-threatening complication after allo-HSCT. Especially with the increasing use of haploidentical allo-HSCT (haplo-HSCT) in the past ten years, PGF and PT have become growing obstacles contributing to high morbidity and mortality after allo-HSCT. A previous clinical prospective cohort study showed that NAC could improve the function of bone marrow endothelial progenitor cells and promote hematopoietic recovery among leukemia patients after haploidentical transplantation. Therefore, we hypothesized that the prophylactic administration of NAC could facilitate the recovery of hematopoietic capacity by improving the bone marrow microenvironment of patients with SAA after haploidentical transplantation.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaojun Huang, M.D.; Phone Number: +861088326006; Email: xjhrm@medmail.com.cn
• Study Contact Backup: Name: Zhengli Xu, M.D.; Phone Number: +8601088326900; Email: xuzhengli0202@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with SAA or vSAA
2. Aged 18-50
3. No severe organ injury
4. No uncontrolled active infections
5. Sign informed consent form, have the ability to comply with study and follow-up procedures

Exclusion Criteria:

1. Hypersensitivity to NAC or history of bronchial asthma
2. Life expectancy less than 30 days post-transplantation
3. Uncontrolled infections pre-transplantation
4. Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
5. Respiratory failure ( PaO2 ≤60mmHg)
6. Hepatic abnormalities (total bilirubin ≥2 times the upper limit of normal [ULN], alanine aminotransferase or aspartate aminotransferase ≥2 times the ULN)
7. Renal dysfunction (creatinine ≥1.5 times the ULN or creatinine clearance rate < 30 mL/min)
8. ECOG performance status ≥3
9. With any conditions not suitable for the trial (investigators' decision)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NAC group; Aplastic anemia patients receiving haploidentical transplantation will be enrolled, and NAC (400mg tid) will be administered orally from day 14 before conditioning until day +60 post-HSCT. The initial dose of NAC was 400mg orally three times daily (TID).

Drug: N Acetyl L Cysteine; For subjects in the experimental intervention arm (NAC group), if the patients met the inclusion criteria on day 14 before conditioning, they received NAC from day 14 before conditioning until day +60 post-HSCT. The initial dose of NAC was 400mg orally three times daily (TID). In cases of grade 3 or worse AEs (not including hematologic recovery), dose modifications including dose reductions or interruptions were permitted at the physician's discretion. After the resolution of AEs, the dose was re-escalated from to 400mg TID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of prolonged thrombcytopenia (PT), which was assessed at +2M post-HSCT.	PT was defined as platelet count less than 20×109/L or a dependence on platelet transfusion with the engraftment of other cell lines(ANC>0.5×109/L and hemoglobin>70 g/L without transfusion support) beyond day +60 post-HSCT in the presence of complete donor chimerism (CDC).	Two months post-HSCT.
The incidence of poor graft function (PGF), which was assessed at +2M post-HSCT.	PGF was defined as the presence of 2 or 3 cytopenic counts (ANC≤0.5×109/L, platelet≤20×109/L, or hemoglobin≤70 g/L) for at least 3 consecutive days beyond day +28 post-HSCT with a transfusion requirement, related with hypoplastic-aplastic BM, in the presence of complete donor chimerism (CDC).	Two months post-HSCT.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The cumulative incidences of transplantation related mortality (TRM).	Number of participants suffered TRM will be calculated.	Two months post-HSCT.
The cumulative incidences of Thrombotic Microangiopathy (TMA).	Number of participants suffered TMA will be calculated.	Two months post-HSCT.
The cumulative incidences of graft versus host disease (GvHD).	Number of participants suffered GvHD will be calculated.	Two months post-HSCT.
The cumulative incidences of overall survival (OS).	Number of participants survived for 1 year post diagnosed will be calculated.	One year post-HSCT.
Adverse reactions	Liver function, renal function, respiratory syndrom assessed by CTCAE v4.0 during oral administration of NAC.	Two months post-HSCT.

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 25, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 29, 2024
• First Submitted That Met QC Criteria: July 20, 2024
• First Posted (Actual): July 24, 2024

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 20, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: HSCT; NAC; hematopoietic recovery
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: NAC in SAA post haplo-HSCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No