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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: T-Cell Acute Lymphoblastic Leukemia; T-Cell Lymphoblastic Lymphoma
• Intervention / Treatment: Drug: Chidamide; Other: Control Group

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yanmin Zhao, MD; Phone Number: 057187236706; Email: yanminzhao@zju.edu.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Chidamide; 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.
Sham Comparator: Control Group; Standard follow-up without maintenance therapy. Regular assessments are performed per the same schedule as the treatment group.	Other: Control Group; Standard follow-up without maintenance therapy. Regular assessments are performed per the same schedule as the treatment group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-Free Survival (RFS)	Time from randomization to the first occurrence of either: (1) disease relapse/progression confirmed by morphology, imaging, or MRD criteria, or (2) death from any cause. Donor lymphocyte infusion (DLI) triggered by MRD elevation is counted as a relapse event. Assessed by Kaplan-Meier method.	From randomization to event, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of Relapse (CIR)	Time from randomization to first relapse/progression, treating non-relapse mortality (NRM) as a competing risk. Analyzed using the Fine-Gray subdistribution hazard model.	From randomization to event, assessed up to 2 years
Overall Survival (OS)	Time from randomization to death from any cause. Assessed by Kaplan-Meier method.	From randomization to event, assessed up to 2 years
Non-Relapse Mortality (NRM)	Time from randomization to death without prior relapse/progression, treating relapse as a competing risk. Analyzed using the Fine-Gray model.	From randomization to event, assessed up to 2 years
Cumulative Incidence of Graft-versus-Host Disease (GVHD)	Cumulative incidence of acute GVHD (graded per MAGIC criteria) and chronic GVHD (graded per NIH 2014/2020 criteria), with death as a competing risk.	From randomization to event, assessed up to 2 years
Incidence of Adverse Events (AEs)	Incidence of all adverse events, treatment-emergent AEs, serious AEs (SAEs), and adverse events of special interest (AESIs, including TA-TMA, VOD/SOS, and CMV/EBV reactivation), graded by NCI-CTCAE v6.0.	From randomization until 28 days after last dose.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Yanmin Zhao, MD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2029

Study Registration Dates

• First Submitted: August 10, 2026
• First Submitted That Met QC Criteria: August 18, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 18, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Chidamide; T-cell lymphoblastic lymphoma; T-cell acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemic and Lymphatic Diseases; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide
• Other Study ID Numbers: CHI-TALL-HSCT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified individual participant data (IPD) for the primary and key secondary outcomes, along with the data dictionary and statistical analysis scripts (R code), will be made available upon reasonable request.

Data sharing will begin 6 to 12 months after publication of the primary results. Requests must include a scientifically valid research proposal and documented ethics approval. A data use agreement will be required. All shared data will be de-identified to protect participant privacy.

Requests should be directed to the principal investigator at the Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine.

• IPD Sharing Time Frame: IPD and supporting information will be available starting 6 months after publication of the primary results and will remain accessible for a period of 12 months.
• IPD Sharing Access Criteria: Access will be granted to researchers who submit a methodologically sound research proposal with a clear analysis plan and documented ethics approval from their institution. The request must be directed to the principal investigator. Approved applicants will receive de-identified individual participant data (IPD), a data dictionary with variable definitions, and fully annotated statistical analysis scripts (R code) to enable replication of the primary and key secondary analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No