Acute Myeloid Leukemia, Adult
Conditions
Brief summary
This prospective, single-center, randomized controlled clinical trial aims to evaluate whether N-acetyl-L-cysteine (NAC) can promote hematopoietic recovery after chemotherapy in patients with acute myeloid leukemia (AML), and to explore its effects on disease remission and bone marrow microenvironment. Eligible participants are newly diagnosed low- or intermediate-risk AML patients aged 18-65 years, with no severe organ dysfunction or active infection. After completing induction chemotherapy with the HAA regimen, subjects will be randomly assigned in a 1:1 ratio to receive either NAC (400 mg orally three times daily for 28 days) plus standard care (intervention group) or standard care alone (control group). A total of 180 patients will be enrolled, with 90 patients in each group. The primary endpoint is the time to platelet recovery, defined as the number of days from the first day of chemotherapy until the first day that platelet count reaches ≥20×10⁹/L and remains stable for 7 consecutive days without transfusion support. Secondary endpoints include time to neutrophil recovery, total dose of G-CSF administered, total volume of red blood cell and platelet transfusions, complete remission rate, relapse-free survival, overall survival, and adverse events. The primary efficacy analysis will be performed in the intention-to-treat (ITT) population. Continuous variables will be compared between groups using the Mann-Whitney U test or paired t-test as appropriate. Safety will be assessed by the incidence and severity of adverse events. All statistical analyses will be conducted using SPSS 22.0, R software, and GraphPad Prism 8. The study is planned to last 3 years to evaluate treatment response and long-term outcomes of patients.
Interventions
N-Acetyl-L-cysteine (NAC) 400 mg oral tablet, three times daily for 28 consecutive days, administered in addition to standard post-induction chemotherapy care for acute myeloid leukemia
Sponsors
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed acute myeloid leukemia (AML, excluding AML-M3) 2. Low-risk or intermediate-risk AML per the 2022 European Leukemia Net (ELN) genetic risk stratification guidelines 3. Aged 18 to 65 years (inclusive) 4. Induction chemotherapy with the HAA regimen. For patients diagnosed with AML harboring FLT3-ITD mutation, treatment with the HAA regimen combined with the FLT3 inhibitor Sorafenib is permitted. 5. No severe organ dysfunction 6. No uncontrolled active infection 7. Signed informed consent, and capable of adhering to study procedures and follow-up protocols
Exclusion criteria
1. Non-remission acute leukemia 2. Hypersensitivity to N-Acetylcysteine (NAC) or a history of bronchial asthma 3. Expected survival of less than 30 days after the end of chemotherapy 4. Uncontrolled infection prior to treatment 5. Cardiac dysfunction (specifically congestive heart failure, unstable coronary artery disease, or severe ventricular arrhythmia requiring antiarrhythmic therapy) 6. Respiratory failure (arterial partial pressure of oxygen PaO₂ ≤ 60 mmHg) 7. Hepatic abnormality: Total serum total bilirubin ≥ 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≥ 2 times ULN 8. Renal abnormality: Serum creatinine ≥ 1.5 times ULN, or creatinine clearance \< 30 mL/min 9. Eastern Cooperative Oncology Group (ECOG) performance status ≥ 3 10. Any other condition unsuitable for trial participation (determined by the investigator)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Platelet Recovery | 60 days post-chemotherapy | The time from Day 1 of chemotherapy until the first day that the platelet count reaches ≥20×10⁹/L and remains stable for 7 consecutive days without transfusion support. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Recovery | 60 days post-chemotherapy | The time from Day 1 of chemotherapy until the first day that the absolute neutrophil count (ANC) reaches ≥0.5×10⁹/L for 3 consecutive days, or the white blood cell (WBC) count reaches ≥1.0×10⁹/L for 3 consecutive days |
| Total Dose of G-CSF | 60 days post-chemotherapy | The total dose of Granulocyte Colony-Stimulating Factor (G-CSF) administered, calculated at a starting dose of 5 µg/kg body weight when the WBC count is \<0.5×10⁹/L, until neutrophil recovery is achieved |
| Total Volume of Platelet Transfusions | 60 days post-chemotherapy | The total volume of platelet transfusions administered after the initiation of chemotherapy, when the platelet count is \<10×10⁹/L |
| Total Volume of Red Blood Cell | 60 days post-chemotherapy | The total volume of red blood cell transfusions administered after the initiation of chemotherapy, when the hemoglobin level is \<70 g/L |
| Complete Remission (CR) Rate | 35 days post chemotherapy | The proportion of patients achieving a best overall response of Complete Remission (CR) as determined by the investigator per ELN guidelines. CR is defined as: Bone marrow (BM) blasts \<5%; no blasts or Auer rods-containing blasts in peripheral blood; no extramedullary disease; Absolute Neutrophil Count (ANC) ≥1.0×10⁹/L; and platelet count ≥100×10⁹/L |
| CR + CRi Rate | 35 days post chemotherapy | The proportion of patients achieving a best overall response of Complete Remission (CR) or Complete Remission with incomplete blood count recovery (CRi) as determined by the investigator per ELN guidelines. CRi is defined as: Bone marrow (BM) blasts \<5%; no blasts or Auer rods-containing blasts in peripheral blood; no extramedullary disease; ANC \<1.0×10⁹/L or platelet count \<100×10⁹/L, and transfusion independence |
| Overall Survival (OS) | 24 months post chemotherapy | The time from diagnosis to death from any cause |
| Relapse-Free Survival (RFS) | 24 months post CR | The time from achieving Complete Remission (CR) until relapse or death from any cause, while maintaining continuous CR status |
| Adverse Events | 30 days after the last dose of NAC | Adverse events related to oral NAC administration, including hepatic function, renal function, or respiratory syndrome evaluated according to the CTCAE version 4.0 |
Contacts
PRINCIPAL_INVESTIGATORXiao-Jun Huang
Peking University People's Hospital
CONTACTXiao-Jun Huang
CONTACTLi-Juan Hu
Outcome results
None listed