Preventing relapse in high-risk T-cell leukemia after stem cell transplant

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 testing if a new combination of medications can help prevent relapse in patients with high-risk T-cell leukemia after they have a stem cell transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 59 (estimated)
• Ages: 14 Years to 55 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT06686108 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the effectiveness of combining demethylating agents, such as azacitidine or decitabine, with venetoclax to prevent relapse in high-risk T-cell lymphoblastic lymphoma/leukemia patients following allogeneic hematopoietic stem cell transplantation. The study compares outcomes of patients receiving this treatment to historical controls who did not receive prophylactic therapy. Key endpoints include relapse-free survival, overall survival, and the incidence of graft-versus-host disease. The goal is to establish a safer and more effective relapse prevention strategy for these patients.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 14-55 with high-risk T-cell lymphoblastic lymphoma/leukemia who have undergone allogeneic hematopoietic stem cell transplantation.

Not a fit: Patients who do not meet the age or health criteria, or those with low-risk disease, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the risk of relapse in high-risk T-cell leukemia patients post-transplant.

How similar studies have performed: While similar approaches have been explored, this specific combination of treatments in this patient population is novel and has not been extensively tested.

Eligibility criteria

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.

Where this trial is running

Shanghai

• Shanghai General Hospital — Shanghai, China (RECRUITING)

Study contacts

• Study coordinator: Xianmin Song

Conditions: T-cell Acute Lymphoblastic Leukemia, ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION, Relapse, T-cell lymphoblastic lymphoma/leukemia, relapse, allogeneic hematopoietic stem cell transplantation