Venetoclax plus azacitidine for newly diagnosed ETP-like and myeloid-mutated T-cell ALL

Evaluating the Efficacy of Venetoclax Combined With Azacitidine Induction Therapy of Early T-cell Precursor-like Acute Lymphoblastic Leukemia and T-ALL With Myeloid Mutations

This trial will try venetoclax combined with azacitidine as first-line treatment for people aged 14 and older with newly diagnosed ETP-like T-ALL, T-ALL with myeloid mutations, or T/myeloid mixed-phenotype leukemia.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07012447 on ClinicalTrials.gov

What this trial studies

This single-arm Phase II trial gives two 28-day induction cycles of oral venetoclax (ramped to 400 mg daily) plus subcutaneous azacitidine (75 mg/m² days 1–7) to newly diagnosed patients with ETP-like ALL, T-ALL with myeloid mutations, or T/My-MPAL. Responses are measured after cycle 1 (days 22–35) and after cycle 2 by bone marrow morphology, flow cytometry, and molecular testing, and overall response rate (CR + CRi) will be compared to historical controls. Patients who do not achieve at least a partial remission after cycle 1 or a CR/CRi after cycle 2 will discontinue protocol therapy and move to alternative consolidation or maintenance as appropriate. Safety is monitored closely under NCI-CTCAE v5.0 with predefined dose modifications and stopping rules.

Who should consider this trial

Good fit: Ideal candidates are people aged 14 or older with newly diagnosed ETP-like ALL, T-ALL harboring myeloid mutations, or T/myeloid mixed-phenotype leukemia who are fit for induction therapy and can attend the trial site.

Not a fit: Patients with relapsed/refractory disease, major organ dysfunction, pregnancy, or those who fail to achieve a partial remission after cycle 1 or CR/CRi after cycle 2 are unlikely to receive benefit from continued protocol therapy.

Why it matters

Potential benefit: If successful, this combination could substantially increase initial remission rates and enable more patients to proceed to potentially curative consolidation such as allogeneic stem cell transplant.

How similar studies have performed: Preclinical data and a small pilot clinical experience indicate venetoclax plus azacitidine can be active in myeloid-like leukemias, but larger confirmatory data in these T-lineage subtypes remain limited.

Eligibility criteria

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

Where this trial is running

Suzhou, Jiangsu

• Ethical Committee of the First Affliated Hospital of Soochow University — Suzhou, Jiangsu, China (RECRUITING)

Study contacts

• Principal investigator: Yue-jun Liu — The First Affiliated Hospital of Soochow University
• Study coordinator: Yue-jun Liu

Conditions: Early T Acute Lymphoblastic Leukemia, T-Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T/Myeloid, Nos, Adverse risk, newly diagnosed, induction therapy