Chidamide Maintenance to Prevent Relapse After Allogeneic Hematopoietic Stem Cell Transplantation in Acute T-Lymphoblastic Leukemia/Lymphoma

Study Design:

This is a prospective, multicenter, open-label, randomized, parallel-group, superiority clinical trial. A total of 132 patients with ETP-phenotype T-ALL/LBL who have achieved complete remission after allo-HSCT will be enrolled.

Intervention:

Chidamide Group: Oral chidamide 10 mg twice weekly (BIW) starting at Day +30 to +100 post-transplant. Treatment cycles are 4 weeks each, for a total of 26 cycles (approximately 24 months). Dose may be escalated to 20 mg BIW in case of MRD positivity.

Control Group: Standard follow-up without maintenance therapy. Regular assessments are performed per the same schedule as the treatment group.

Study Assessments:

Efficacy: Relapse-free survival (RFS), cumulative incidence of relapse (CIR), overall survival (OS), non-relapse mortality (NRM).

Safety: Adverse events graded by NCI-CTCAE v6.0, including hematologic toxicity, infections, and transplant-related complications (TA-TMA, VOD/SOS, etc.).

GVHD: Acute GVHD graded per MAGIC criteria, chronic GVHD per NIH 2014/2020 criteria.

Exploratory: Minimal/measurable residual disease (MRD) dynamics by multi-parameter flow cytometry (MFC) or qPCR/NGS; immune reconstitution (T/B/NK/Treg subsets); cytokine/chemokine profiling; patient-reported outcomes (EQ-5D-5L, FACT-BMT); and health economic evaluation.

Follow-up:

Patients will be followed for at least 24 months after the last patient is enrolled. The total study duration is expected to be approximately 4 years.

Statistical Analysis:

The primary analysis will be performed on the modified intention-to-treat (mITT) population. RFS will be estimated using the Kaplan-Meier method and compared by log-rank test. A Cox proportional hazards model will be used to estimate hazard ratios (HR) with 95% confidence intervals (CI). For competing risk events (e.g., NRM for CIR), the Fine-Gray subdistribution hazard model will be applied. Sensitivity analyses will be conducted to assess robustness.

Sample Size:

Based on Schoenfeld's formula for log-rank test, assuming a 2-year RFS of 55% in the control group and 75% in the chidamide group (HR ≈ 0.48), with a two-sided alpha of 0.05, power of 80%, and 1:1 allocation, approximately 59 events are required. Accounting for a 5% dropout rate, the total sample size is 132 patients (66 per group).

Inclusion criteria

• Age 14-70 years (inclusive).
• Confirmed diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) according to the 2016 WHO classification, with an early T-cell precursor (ETP) phenotype defined by immunophenotypic criteria: CD1a-, CD8-, CD5 weak, with expression of one or more myeloid/stem cell markers (e.g., CD34, CD117, HLA-DR, CD13, CD33, CD11b, or CD65).
• Have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) and achieved complete remission (CR/CRh/CRi) with full donor chimerism (≥95% by STR or equivalent method).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate organ function:

• Creatinine clearance ≥60 mL/min (Cockcroft-Gault).
• AST and ALT ≤3×ULN; total bilirubin ≤2×ULN (≤3×ULN for Gilbert's syndrome).
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiography.
• Life expectancy >8 weeks.
• Willing and able to provide written informed consent and comply with study procedures.
• For women of childbearing potential: negative serum/urine pregnancy test at baseline; and agreement to use highly effective contraception during treatment and for at least 6 months after the last dose.

Exclusion criteria

• Evidence of relapse or disease progression at screening or baseline.
• Persistent significant myelosuppression (ANC <1.0×10⁹/L or platelets <25×10⁹/L within 7 days without transfusion support) unrelated to reversible causes.
• Active grade 3-4 acute GVHD, or acute GVHD requiring systemic corticosteroids ≥0.5 mg/kg/day prednisone equivalent to control; or active moderate-severe chronic GVHD not well controlled by standard therapy.
• Active autoimmune disease requiring systemic immunosuppression.
• Clinically significant cardiovascular disease: uncontrolled arrhythmia, QTc prolongation >470 ms (males) or >480 ms (females), uncontrolled hypertension ≥160/100 mmHg, NYHA class III-IV heart failure, or acute myocardial infarction/unstable angina within 6 months.
• Uncontrolled infections or other severe medical conditions that would increase study risk.
• Uncontrolled chronic viral infections: HIV positive; HBV (HBsAg positive with HBV-DNA >ULN or not on antiviral therapy); HCV (anti-HCV positive with HCV RNA >ULN or not on antiviral therapy).
• Pregnancy or breastfeeding, or unwillingness to use effective contraception.
• Gastrointestinal disorders affecting oral drug absorption.
• Inability to understand or comply with study requirements.
• Use of other HDAC inhibitors or investigational anticancer agents within 14 days prior to randomization; use of strong CYP inducers/inhibitors that may significantly alter chidamide exposure; or live vaccination within 4 weeks before baseline.