Venetoclax + Azacytidine for Newly Diagnosed ETP-like ALL and T-ALL With Myeloid Mutations

Summary

The goal of this clinical trial is to evaluate the efficacy and safety of venetoclax combined with azacitidine in treating newly diagnosed early T-cell precursor (ETP)-like acute lymphoblastic leukemia (ALL), T-ALL with myeloid mutations, or T/myeloid mixed-phenotype acute leukemia (T/My-MPAL). Participant population: Patients aged ≥14 years diagnosed with ETP-like leukemia, T-ALL with myeloid mutations, or T/My-MPAL, regardless of sex/gender. The main question it aims to answer: Does venetoclax plus azacitidine achieve a significantly higher overall response rate (ORR: CR + CRi) compared to historical controls (54% vs. 90%) after two induction cycles? Comparison group: Researchers will compare ORR outcomes to historical data from conventional chemotherapy regimens to assess treatment superiority. Participants will: * Receive two 28-day cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m²/day SC, D1-7). * Undergo serial bone marrow biopsies, blood tests, and imaging (e.g., PET-CT) for response assessment. * Follow dose adjustment protocols for toxicity management (e.g., neutropenia, thrombocytopenia).

Eligibility

Inclusion Criteria:

1. No gender restrictions
2. Age ≥ 14 years
3. Confirmed diagnosis of one of the following:

   ETP-like leukemia (CD7⁺, CD1a-, CD8-, with CD5 expression stratified as ETP-ALL ≤75% or Near-ETP-ALL \>75%) T-cell acute lymphoblastic leukemia (T-ALL) with myeloid mutations (including FLT3, DNMT3A, STAG2, IDH1/2, RUNX1, EZH2, WT1, ASXL1/2, SF3B1, TET2, BCOR, BCORL1, and MLL-PTD) T/myeloid mixed phenotype acute leukemia (T/My-MPAL) (with concurrent T-lineage and myeloid markers, e.g., cCD3⁺/mCD3⁺, CD7⁺, MPO⁺)
4. Newly diagnosed patients without prior induction therapy Limited prior therapy allowed: hydroxyurea, dexamethasone, or low-dose cytarabine/venetoclax (cumulative dose \<0.5g), and leukocytapheresis
5. Expected survival time ≥ 3 months
6. Liver function: total bilirubin ≤ 2× ULN; ALT/AST ≤ 3× ULN (or ≤ 5× ULN if liver infiltration by leukemia is present) ; Renal function: endogenous creatinine clearance ≥ 30 ml/min; Cardiac function: left ventricular ejection fraction \> 45%
7. Demonstrated capacity to understand the study and willingness to provide informed consent

Exclusion Criteria:

1. Presence of recurrent genetic abnormalities such as t(8;21), t(15;17), inv(16)/t(16;16) leukemia
2. Prior hypersensitivity to study drugs or compounds of similar chemical structure
3. Active uncontrolled infections as determined by the investigator
4. Active bleeding
5. Recent history (within 1 year) of thrombosis, embolism, or cerebral hemorrhage
6. Pregnancy, breastfeeding, or unwillingness to use contraception in women of childbearing potential
7. Drug addiction or chronic alcoholism that could interfere with trial evaluation
8. Psychiatric disorders or other conditions that would prevent obtaining informed consent or compliance with trial requirements
9. Any condition deemed unsuitable for trial participation by the investigator

Conditions4

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