Demethylating Agents Combined with Venetoclax for High-risk T-Cell Lymphoma/leukemia Post-Transplant Relapse Prevention
- Registration Number
- NCT06686108
- 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.
- 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.
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Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 59
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.
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- Accepting other investigational drugs.
- 14.According to the researchers' assessment, the patient may have complications that could lead to other dangers.
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Exclusion Criteria
Not provided
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description combination therapy Azacitidine (AZA) Days 1 - 5 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. combination therapy Decitabine (DAC) 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. combination therapy Venetoclax 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.
- Primary Outcome Measures
Name Time Method RFS 2 year 2-year relapse-free survival
- Secondary Outcome Measures
Name Time Method CIR 2 year 2-year cumulative incidence of relapse
OS 2 year 2-year overall survival
GRFS 2 year 2-year graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) rates
cGVHD 2 year 2-year cumulative incidence of cGVHD
adverse events at the end of every cycle (each cycle is 28 days) adverse events during research
Trial Locations
- Locations (1)
Shanghai General Hospital
🇨🇳Shanghai, China