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

NCT06686108 | Recruiting Phase 2 FDA Drug

• 1 other identifier: SHSYXY-T-LBL-AZA/VEN-Rel-2024
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

T-cell Acute Lymphoblastic Leukemia; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; Relapse

Keywords

T-cell lymphoblastic lymphoma/leukemia; relapse; allogeneic hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• RFS

  1-year relapse-free survival

  1 year

• RFS

  2-year relapse-free survival

  2 year

Secondary Outcomes (9)

• CIR

  1 year

• CIR

  2 year

• OS

  1 year

• OS

  2 year

• GRFS

  1 year

Study Arms (1)

combination therapy

EXPERIMENTAL

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; Drug: Decitabine (DAC); Drug: Venetoclax

Interventions

Azacitidine (AZA) Days 1 - 5 DRUG

Azacitidine, ih, 32mg/m2/d, days 1-5 of each 28-day cycle

combination therapy

Decitabine (DAC) DRUG

decitabine, 5mg/m2/d, days 1-5 of each 28-day cycle.

combination therapy

Venetoclax DRUG

venetoclax, 400mg/d, days 1-7 of each 28-day cycle

combination therapy

Eligibility Criteria

• Age: 14 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years old, male,or female.
• Patients with allo-HSCT due to T-LBL/ALL, the donor type is not limited.
• ECOG score is 0-2 points.
• Blood routine: ANC ≥ 1.0 × 109/L, PLT ≥ 50 × 109/L.
• 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.

You may not qualify if:

• Central involvement during any course of the disease.
• Patients who have not achieved complete remission before transplantation.
• Identify those with available targeted drugs.
• 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.
• Individuals who are known to be allergic to demethylating drugs or venetoclax.
• Individuals with grade 2 or more degrees of active acute GVHD.
• Individuals with moderate to severe chronic GVHD.
• 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%.
• Blood routine: ANC\<1.0 × 109/L or PLT\<50 × 109/L.
• 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.
• Merge severe active infections.
• Pregnant or lactating women.
• \. Accepting other investigational drugs.
• According to the researchers' assessment, the patient may have complications that could lead to other dangers.

Sponsors & Collaborators

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

Study Sites (1)

Shanghai General Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Leukemia

Interventions

Azacitidine; Decitabine; venetoclax

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Xianmin Song

CONTACT

+8613501672508; shongxm@139.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 13, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2028
• Last Updated: May 7, 2025

Record last verified: 2024-10

Locations

CN (1)