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

Chidamide Maintenance to Prevent Relapse After Allogeneic HSCT in Acute T-Lymphoblastic Leukemia/Lymphoma: A Multicenter Randomized Controlled Trial

This study evaluates whether chidamide maintenance therapy can effectively reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with high-risk T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma (T-ALL/LBL). Chidamide is an oral selective histone deacetylase inhibitor (HDACi) with dual anti-tumor and immunomodulatory effects.

Participants will be randomized in a 1:1 ratio to receive either chidamide maintenance for up to 24 months or standard follow-up without maintenance. The primary endpoint is relapse-free survival (RFS). Key secondary endpoints include cumulative incidence of relapse (CIR), overall survival (OS), non-relapse mortality (NRM), incidence and severity of graft-versus-host disease (GVHD), safety profile, and patient-reported outcomes (PROs).

This multicenter, open-label, randomized controlled trial aims to provide high-level evidence on the efficacy and safety of chidamide as a post-transplant maintenance strategy. Approximately 132 patients will be enrolled across 6 transplant centers in China.

Inclusion Criteria:

1. Age 14-70 years (inclusive).

2. 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).

3. 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).

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

5. 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.

6. Life expectancy >8 weeks.

7. Willing and able to provide written informed consent and comply with study procedures.

8. 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:

1. Evidence of relapse or disease progression at screening or baseline.
2. Persistent significant myelosuppression (ANC <1.0×10⁹/L or platelets <25×10⁹/L within 7 days without transfusion support) unrelated to reversible causes.
3. 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.
4. Active autoimmune disease requiring systemic immunosuppression.
5. 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.
6. Uncontrolled infections or other severe medical conditions that would increase study risk.
7. 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).
8. Pregnancy or breastfeeding, or unwillingness to use effective contraception.
9. Gastrointestinal disorders affecting oral drug absorption.
10. Inability to understand or comply with study requirements.
11. 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.