Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL

Overview

This is a prospective, open-label, randomized controlled trial to evaluate the efficacy and safety of low-intensity chemotherapy combined with targeted agents (venetoclax and blinatumomab) in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Patients will be randomized to receive or not receive venetoclax during the first three cycles of induction and consolidation therapy. All patients receive olverembatinib (a third-generation TKI) continuously and may receive up to 4 cycles of blinatumomab starting from the fourth cycle. The primary endpoint is the rate of BCR::ABL1 ≤0.01% at 90 days and event-free survival (EFS). Secondary endpoints include overall survival (OS), relapse-free survival (RFS), molecular relapse rate, MRD negativity rate by NGS, and cardiovascular events.

Background: Ph+ ALL is a high-risk subtype of adult ALL. Although outcomes have improved with TKI-based therapy, achieving early deep molecular response remains critical for long-term survival. Novel combinations with BCL2 inhibitor venetoclax and CD3-CD19 bispecific antibody blinatumomab may further deepen responses. Objective: To determine whether adding venetoclax to a low-intensity chemotherapy backbone (vincristine, prednisone, olverembatinib) improves early molecular response and survival, and to explore the impact of different cycles of blinatumomab. Design: This is a single-center, open-label, randomized controlled trial. Eligible patients are newly diagnosed Ph+ ALL aged ≥14 years, with ECOG ≤2 and adequate organ function. Patients will be randomized 1:1 to Arm A (control) or Arm B (venetoclax) during the first three cycles.