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

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.

Eligibility

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.

Conditions4

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