NCT07012447

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Sponsor: yuejun Liu · Academic / Other
• Sex: All
• Age: 14 Years
• Healthy volunteers: Not accepted

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).

Detailed description

This study addresses the unmet need for effective therapies in high-risk T-ALL subtypes, including ETP-like leukemia and T/My-MPAL, which exhibit myeloid-like genetic profiles (e.g., FLT3, DNMT3A, RUNX1 mutations) and poor outcomes under conventional chemotherapy (5-year OS \<40%). Preclinical and pilot clinical data demonstrate that venetoclax, a BCL-2 inhibitor, synergizes with azacitidine, a hypomethylating agent, to induce apoptosis in leukemia stem cells by targeting oxidative phosphorylation and epigenetic dysregulation. Building on a pilot study, this Phase II trial employs a single-arm design to validate efficacy in a larger cohort. Patients receive two induction cycles of venetoclax (oral, 100 mg D1, 200 mg D2, 400 mg D3-28) and azacitidine (75 mg/m² SC D1-7), with response assessed via bone marrow morphology, flow cytometry, and molecular testing (Days 22-35). Early Efficacy Evaluation: After the first induction cycle (Days 22-35), response is assessed via bone marrow morphology, flow cytometry, and molecular profiling. Stopping Criteria: Patients failing to achieve at least partial remission (PR) after Cycle 1 will be withdrawn from the study. Patients failing to achieve CR or CRi at the end of Cycle 2 will also discontinue study treatment. Consolidation strategies include allo-HSCT or high dose cytarabine (HiDAC) for fit patients or maintenance therapy for unfit individuals. Rigorous safety monitoring follows NCI-CTCAE v5.0 criteria, with dose adjustments for hematologic/non-hematologic toxicities. Statistical analysis includes intent-to-treat and per-protocol populations, with ORR analyzed via exact binomial tests and survival endpoints via Kaplan-Meier/Cox regression. The study integrates translational biomarkers (e.g., BCL-2 expression, mutational profiling) to identify predictors of response, aiming to establish a novel, mechanism-driven regimen for these aggressive leukemias.

Conditions

• Early T Acute Lymphoblastic Leukemia
• T-Acute Lymphoblastic Leukemia
• Mixed Phenotype Acute Leukemia, T/Myeloid, Nos

Interventions

Type	Name	Description
DRUG	Venetoclax	Orally by mouth
DRUG	Azacitidine	Subcutaneous injection
DRUG	Cytarabine	Intravenous infusion

Timeline

• Start date: 2025-04-01
• Primary completion: 2027-04-01
• Completion: 2028-05-01
• First posted: 2025-06-10
• Last updated: 2025-06-10

Locations

1 site across 1 country: China