Overview
This is a prospective, open-label, randomized controlled trial to evaluate the efficacy of low-intensity chemotherapy combined with 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.
Description
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.
Eligibility
Inclusion Criteria:
- Newly diagnosed ALL with t(9;22)(q34;q11) or BCR::ABL1 positivity (by PCR or FISH).
- Age ≥ 14 years.
- ECOG performance status ≤ 2.
- Adequate organ function: Total bilirubin \<1.5x ULN; AST/ALT ≤2.5x ULN; Serum creatinine \<2x ULN; Cardiac enzymes \<2x ULN; Serum amylase ≤1.5x ULN; Left ventricular ejection fraction (LVEF) \>45%.
- Male and female patients of childbearing potential must agree to use effective contraception.
- Signed informed consent.
Exclusion Criteria:
- Diagnosis of chronic myeloid leukemia in chronic, accelerated, or blast phase.
- Prior systemic anti-leukemic therapy for ALL (except corticosteroids or hydroxyurea for cytoreduction prior to enrollment).
- Myocardial infarction within 12 months prior to enrollment; uncontrolled/unstable angina, congestive heart failure, uncontrolled hypertension or arrhythmia.
- Uncontrolled active severe infection.
- Active psychiatric illness that may hinder treatment completion or informed consent.
- Any other condition deemed unsuitable for the study by the investigator.
