Low-dose Chidamide Maintenance Therapy After Allo-HSCT for T-cell Acute Lymphoblastic Leukemia or T-cell Lymphomas

A Phase ll,Single-center,Single-arm Clinical Study of Low-dose Chidamide Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for T-cell Acute Lymphoblastic Leukemia or T-cell Lymphomas

Clinical Study on the Safety and Effectiveness of low-dose chidamide maintenance therapy after allogeneic hematopoietic stem cell transplantation for T-cell acute lymphoblastic leukemia or T-cell lymphomas.

Study Overview

• Status: Recruiting
• Conditions: T Lymphoblastic Leukemia/Lymphoma
• Intervention / Treatment: Drug: Chidamide

Detailed Description

This is a phase ll, single-center, single-arm clinical study.This study is indicated for high-risk of T-cell acute lymphoblastic leukemia or T-cell lymphomas patients. It aims to evaluate the safety and effectiveness of low-dose chidamide maintenance therapy after allogeneic hematopoietic stem cell transplantation for T-cell acute lymphoblastic leukemia or T-cell lymphomas to prevent relapse. 44 patients will be enrolled. The clinical end points include relapse-free survival, acute or chronic GVHD, non-relapse mortality, and overall survival, etc.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yanmin Zhao, PhD; Phone Number: +8615858199217; Email: yanminzhao@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Recruiting
      • The First Hospital of Zhejiang Medical Colleage Zhejiang University
      • Contact: Yanmin Zhao, PhD; Phone Number: +8615858199217; Email: yanminzhao@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. T-cell acute lymphoblastic leukemia or T-cell lymphomas (mainly including peripheral T-cell lymphoma, NK/T-cell lymphoma, T-lymphoblastic lymphoma, etc.) must be diagnosed before enrollment. The diagnostic criteria refer to the 2016 WHO classification. Patients is in high-risk group or standard-risk group with MRD-positive patients after transplantation.
2. Age 14-70;
3. Stable hematopoietic reconstitution 90±10 days after receiving allogeneic hematopoietic stem cell transplantation, no aGVHD or stable aGVHD control and stable primary disease;
4. Complete donor chimerism after transplantation;
5. During the screening period after transplantation (within 4 weeks before Chidanilide administration), the primary disease is remission and MRD is negative.
6. Eastern Cooperative Oncology Group (ECOG) physical condition score is 0-2 points;
7. Creatinine clearance ≥ 60 mL/min (according to the Cockcroft-Gault formula);
8. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal range (ULN), total bilirubin ≤ 2 × ULN;
9. Echocardiography (ECHO) shows left ventricular ejection fraction (LVEF) ≥ 50%
10. Life expectancy >8 weeks;
11. Voluntarily sign the informed consent form, understand and comply with the requirements of the research.

Exclusion Criteria:

1. Bone marrow recurrence or extramedullary recurrence after transplantation;
2. Hemocytopenia after transplantation: white blood cells <2000/ul, platelets <25000/ul;
3. Active grade 3-4 acute GVHD, or active moderate-to-severe chronic GVHD that cannot be controlled by drugs;
4. Active autoimmune diseases, such as SLE, rheumatoid arthritis, etc.;
5. Currently suffering from clinically significant active cardiovascular disease, such as uncontrolled arrhythmia, prolonged QTc interval of electrocardiogram, uncontrolled uncontrolled hypertension, congestive heart failure, any New York Heart Association (NYHA) functional class 3 or 4 cardiac disease, or a history of myocardial infarction within 6 months before screening;
6. Other serious diseases that may limit patients to participate in this trial (such as advanced infection, uncontrolled diabetes, renal failure);
7. Known human immunodeficiency virus (HIV) infection, or hepatitis B virus that cannot be controlled by drugs (HBV-DNA positive, and HBV DNA test value above the upper limit of normal value) or hepatitis C virus (anti-HCV positive, and HCV viral titer detection value above the upper limit of normal value) Chronic Infect;
8. Pregnant or lactating women;
9. Those who cannot understand and follow the research protocol or cannot sign the informed consent form;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: low-dose chidamide maintenance therapy after allo-HSCT	Drug: Chidamide; In the time window of 30-180 days after transplantation: oral chidamide 10mg twice a week with a total of 96 courses(4 weeks as a course). If the MRD turns positive during treatment, the dose can be increased to a maximum of 20 mg twice a week, and donor lymphocyte infusion (DLI) is also permitted in the case of MRD positivity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival(RFS)	The time from the date of treatment to the occurrence of any of the following: Death from any cause; Disease recurrence, defined as one of the following: Leukemia blasts reappeared in peripheral blood, or blasts ≥ 5%, naive monocytes ≥ 5% in bone marrow, or extramedullary lesions.	At Year 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft-versus-host disease (GVHD)	Acute GVHD or chronic GVHD incidence after chidamide maintenance therapy	At Year 2
Adverse effects	Drug related adverse effects after chidamide maintenance therapy	At Year 2
Measurable residual disease(MRD) status		At Year 2
Changes in t lymphocyte subsets		At Year 2
Non-relapse mortality (NRM)	Assessment of NRM at Year 2	At Year 2
GVHD-free-relapse-free survival(GRFS)	Assessment of GRFS at Year 2	At Year 2
Overall survival (OS)	Assessment of OS at Year 2	At Year 2

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: July 23, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: allo-HSCT; chidamide; maintenance therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, T-Cell; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: IIT20230004C-R2

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