Pediatric-Inspired Regimen Combined With Venetoclax and Immunotherapy for Adult Ph-Negative Acute Lymphoblastic Leukemia

A Prospective Cohort Study of a Pediatric-Inspired Chemotherapy Regimen Combined With Venetoclax and Immunotherapy for the Treatment of Adult Ph-Negative Acute Lymphoblastic Leukemia

This is a prospective, open-label, non-randomized cohort study evaluating the efficacy and safety of a pediatric-inspired chemotherapy regimen (IH-2014 based) combined with venetoclax and immunotherapy in adult patients with newly diagnosed Ph-negative Acute Lymphoblastic Leukemia (ALL). Patients aged ≥14years,≤60 years will be enrolled. Treatment includes induction, consolidation, early intensification, delayed intensification, and maintenance phases. The use and number of cycles of immunotherapy will be based on patient preference. The primary endpoint is Event-Free Survival (EFS) and MRD-negative CR rates after induction therapy(by flow cytometry and NGS). Secondary endpoints include Complete Remission (CR) rate, MRD-negative CR rates at 12 weeks (by flow cytometry and NGS), Overall Survival (OS), Relapse-Free Survival (RFS), and cumulative relapse rate.

Adult Ph-negative ALL has inferior outcomes compared to childhood ALL. Pediatric-inspired regimens have improved survival in adolescent and young adult (AYA) patients. Venetoclax, a BCL-2 inhibitor, has shown preclinical sensitivity in Ph-negative ALL. Our center's previous IH-2022 regimen (a pediatric-inspired regimen combined with venetoclax protocol) showed promising efficacy and tolerability in adult patients.Immunotherapy is effective in ALL. This study aims to integrate immunotherapy into the pediatric-inspired backbone to optimize the regimen and improve survival outcomes.

Inclusion Criteria:

• Newly diagnosed, previously untreated (except prednisone/hydroxyurea) Ph-negative ALL
• Age ≥14 years, ≤60 years
• ECOG performance status ≤2
• Adequate organ function (liver, kidney, cardiac)
• For patients of childbearing potential: use of effective contraception
• Willing and able to provide informed consent

Exclusion Criteria:

• Burkitt leukemia/lymphoma
• Acute leukemia of ambiguous lineage
• Pregnancy or lactation
• Severe uncontrolled active infection
• History of pancreatitis
• Uncontrolled diabetes (HbA1c >7.5%)
• Active gastrointestinal bleeding within 6 months
• Arterial/venous thrombosis within 6 months
• Known HIV positivity
• Severe psychiatric illness hindering compliance
• Any other condition deemed unsuitable by the investigator