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

Launched by SHANGHAI GENERAL HOSPITAL, SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE · Nov 11, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with high-risk T-cell lymphoma or leukemia who have had a stem cell transplant. The goal of the study is to see if combining two medications, called demethylating agents and venetoclax, can help prevent the cancer from coming back after the transplant. The trial is currently recruiting participants aged 14 to 55 who have undergone an allogeneic stem cell transplant due to T-cell lymphoma or leukemia and have specific high-risk factors related to their disease.

To be eligible for this trial, patients must have had a transplant and show certain signs that put them at higher risk for relapse, like older age at diagnosis or specific lab results. Participants can expect to receive the new treatment and be monitored closely by the research team for any side effects or improvements in their condition. It's also important to know that some patients may not qualify for the trial if they have ongoing infections or other serious health issues.

Gender

ALL

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.