Demethylating Agents Combined With Venetoclax for High-risk T-cell Lymphoblastic Lymphoma/Leukemia Post-Transplant Relapse Prevention

Safety and Efficacy Study of Demethylating Agents With Venetoclax in Preventing Recurrence of High-risk T-cell Lymphoblastic Lymphoma/Leukemia After Transplantation

This study is a prospective, phase II clinical trial with the primary objective of assessing the effectiveness of demethylating agents combined with venetoclax in the prevention of recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) of high risk T-lymphoblastic lymphoma/leukemia (T-LBL/ALL) patients.

Study Overview

• Status: Recruiting
• Conditions: Relapse; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; T-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Azacitidine (AZA) Days 1 - 5; Drug: Decitabine (DAC); Drug: Venetoclax

Detailed Description

The experimental group included high risk T-ALL/LBL patients after allo-HSCT, who received relapse prevention treatment with demethylating agents such as azacitidine or decitabine, combined with venetoclax.

The historical control consisted of high-risk T-ALL/LBL patients who received allo-HSCT but did not receive any prophylactic treatment from multiple centers, and their basic information, disease information, treatment details, and efficacy data were collected. Propensity score matching was conducted with historical data to compare the advantages and disadvantages of the experimental regimen with the control group.

The primary endpoint was the relapse-free survival(RFS) rate after prophylaxis, while secondary endpoints included cumulative incidence of relapse (CIR), overall survival (OS), and the GVHD-relapse-free survival (GRFS). This study aims to provide a effective and safer prophylaxis treatment for high-risk T-LBL/ALL patients after all-HSCT.

• Study Type: Interventional
• Enrollment (Estimated): 59
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xianmin Song; Phone Number: +8613501672508; Email: shongxm@139.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai General Hospital
    • Contact: Xianmin Song; Phone Number: +8613501672508; Email: shongxm@139.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.14-55 years old, male,or female.
• 2.Patients with allo-HSCT due to T-LBL/ALL, the donor type is not limited.
• 3.ECOG score is 0-2 points.
• 4.Blood routine: ANC ≥ 1.0 × 109/L, PLT ≥ 50 × 109/L.
• 5.One of the following high-risk factors:
• a. Age of initial diagnosis ≥ 35 years old.
• b. Initial diagnosis of WBC ≥ 100 × 109/L.
• c. Initial diagnosis of LDH exceeding the upper limit of normal values.
• d. Initial diagnosis of bone marrow involvement (blast cells ≥ 5%).
• e. Initial diagnosis of a bulky in the mediastinum (longest diameter ≥ 10cm).
• f. ETP immunophenotype.
• g. During the induction chemotherapy process, 2 courses did not achieve partial remission and/or 4 courses did not achieve complete remission.
• h. Residual lesions before transplantation: Flow cytometry analysis showed that the proportion of abnormal lymphoid cells in the bone marrow was greater than 0.01%; Positive detection of minimal residual lesions in molecular biology; PET-CT scan shows that residual lesions are still active.
• i. Based on the ELN recommendation based on adult T-ALL: gene mutations involving myeloid related genes, RAS/PI3K/AKT, JAK/STAT signaling pathway, and epigenetics, such as FLT3, NRAS/KRAS, PTEN, IL7R, JAK1, JAK3, DNMT3A, IDH1, IDH2; TP53, BCL2 mutations; t (8; 14) (q24; q11)/MYC rearrangement; t (7; 19) (q34; p13)/TCR-LYL1，TCR-MEF2C; del(5q) (q14).
• j. High risk subgroups based on NGS definition: PI3K signaling pathway/NRAS, KRAS/TP53/IKZF1/DNTM3A/IDH1, IDH2 gene mutation with or without NOTCH1, FBXW7/PHF6/EP300 gene mutation.

Exclusion Criteria：

• 1.Central involvement during any course of the disease.
• 2.Patients who have not achieved complete remission before transplantation.
• 3.Identify those with available targeted drugs.
• 4.For those who are resistant to BCL-2 inhibitors before transplantation, if the disease progresses during the application process, or if 3-4 courses of induction therapy containing BCL2 inhibitors do not improve.
• 5.Individuals who are known to be allergic to demethylating drugs or venetoclax.
• 6.Individuals with grade 2 or more degrees of active acute GVHD.
• 7.Individuals with moderate to severe chronic GVHD.
• 8.T-LBL/ALL relapse (flow cytometry abnormal lymphocyte cell proportion>0.01%, WT1 positive, fusion gene positive, or extramedullary recurrence), or transplant rejection, bone marrow donor cell chimerism<95%.
• 9.Blood routine: ANC<1.0 × 109/L or PLT<50 × 109/L.
• 10.Combined with severe organ dysfunction; The ratio of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) is more than 3 times the normal value or the normal value of direct bilirubin is more than 3 times; The endogenous creatinine clearance rate (Ccr) is less than 50mL/min or 1.5 times the normal value of blood creatinine, regardless of whether hemodialysis treatment is used.
• 11.Merge severe active infections.
• 12.Pregnant or lactating women.
• 13. Accepting other investigational drugs.
• 14.According to the researchers' assessment, the patient may have complications that could lead to other dangers.

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: combination therapy; There is only 1 arm. Combination therapy arm included venetoclax combined with hypomethylating agents such as azacitidine or decitabine. 1. venetoclax: 400mg/d, po, days 1-7 of each 28-day cycle. 2.For patients without TP53 mutation, azacitidine was administered: 32mg/m2/d, ih, days 1-5 of each 28-day cycle; for patients with TP53 mutation, decitabine was administered: 5mg/m2/d, iv, days 1-5 of each 28-day cycle.

Drug: Azacitidine (AZA) Days 1 - 5; Azacitidine, ih, 32mg/m2/d, days 1-5 of each 28-day cycle; Drug: Decitabine (DAC); decitabine, 5mg/m2/d, days 1-5 of each 28-day cycle.; Drug: Venetoclax; venetoclax, 400mg/d, days 1-7 of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RFS	1-year relapse-free survival	1 year
RFS	2-year relapse-free survival	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CIR	1-year cumulative incidence of relapse	1 year
CIR	2-year cumulative incidence of relapse	2 year
OS	1-year overall survival	1 year
OS	2-year overall survival	2 year
GRFS	1-year graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates	1 year
GRFS	2-year graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates	2 year
cGVHD	1-year cumulative incidence of cGVHD	1 year
cGVHD	2-year cumulative incidence of cGVHD	2 year
adverse events	adverse events during research	at the end of every cycle (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2028

Study Registration Dates

• First Submitted: November 11, 2024
• First Submitted That Met QC Criteria: November 11, 2024
• First Posted (Actual): November 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 4, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: relapse; allogeneic hematopoietic stem cell transplantation; T-cell lymphoblastic lymphoma/leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Recurrence; Leukemia; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Decitabine; Venetoclax; Azacitidine
• Other Study ID Numbers: SHSYXY-T-LBL-AZA/VEN-Rel-2024

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes