新诊断成人 Ph 阴性 B-ALL 的免疫靶向治疗联合低剂量化疗前瞻性伞式试验

Inclusion Criteria:

1. Newly diagnosed adult (≥18 years) patients with Ph-negative B-cell acute lymphoblastic leukemia according to WHO 2022 criteria.
2. CD22-positive expression on tumor cells (CD22 ≥20%).
3. Expected survival ≥3 months.
4. Sexually active men and women of childbearing potential must agree to use effective contraception.
5. Ability to understand and voluntarily sign informed consent, and willingness to comply with study requirements. Informed consent must be signed by the patient or a legal next of kin prior to initiation of any study-specific procedures.

Exclusion Criteria:

1. Burkitt lymphoma/leukemia.
2. Acute leukemia of ambiguous lineage.
3. Pregnant women.
4. Severe, uncontrolled active infections.
5. History of chronic liver disease (e.g., liver cirrhosis) or prior veno-occlusive disease (VOD) / sinusoidal obstruction syndrome (SOS).
6. History of clinically significant ventricular arrhythmias, unexplained syncope (not vasovagal), or sinus node dysfunction or high-grade atrioventricular (AV) block with chronic bradycardia, unless a permanent pacemaker has been implanted.
7. Uncontrolled active hepatitis B or hepatitis C infection, or known HIV seropositivity. HIV testing may be required according to local regulations or standards.
8. Psychiatric disorders that may impair the subject's ability to complete treatment or provide informed consent.
9. Any other conditions deemed by the investigator to render the subject unsuitable for participation in the study.

主要终点：Flow Cytometric MRD-Negative Complete Remission Rate · Proportion of patients achieving complete remission (CR) with negative measurable residual disease (MRD) assessed by multiparameter flow cytometry after completion of induction therapy. · At the end of induction therapy (approximately 1 month after treatment initiation)
次要终点：Next-Generation Sequencing (NGS)-MRD Negative Remission Rate；Best MRD Clearance Rate；Overall Survival (OS)；Disease-Free Survival (DFS)；Relapse-Free Survival (RFS)；30-Day Mortality；60-Day Mortality；Incidence of Adverse Events

• Immuno-Targeted Therapy Plus Low-Dose Chemotherapy · EXPERIMENTAL · Adult patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph- B-ALL) receive frontline treatment with immuno-targeted agents, a BCL2 inhibitor, and low-dose chemotherapy. Induction therapy includes inotuzumab ozogamicin, venetoclax, vincristine, cyclophosphamide, and dexamethasone. Subsequent treatment is adapted according to measurable residual disease (MRD) response, antigen expression profile, and clinical condition, and may include blinatumomab-based immunotherapy, venetoclax-containing chemotherapy, CD19-directed CAR-T cell therapy, or hematopoietic stem cell transplantation. All patients proceed to protocol-defined maintenance therapy.

This is a prospective, open-label, single-arm, umbrella phase 2 clinical trial enrolling 32 adult patients with newly diagnosed Philadelphia chromosome-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL). All patients receive a frontline treatment backbone consisting of low-dose chemotherapy combined with immuno-targeted agents and a BCL2 inhibitor. Subsequent treatment pathways are guided by MRD response, disease characteristics, and clinical decision-making, including antibody-based immunotherapy, CAR-T cell therapy, or hematopoietic stem cell transplantation. All patients continue protocol-defined maintenance therapy after consolidation. The primary endpoint is the complete remission rate with negative flow cytometric MRD after induction therapy. MRD is monitored longitudinally by flow cytometry, quantitative PCR, and immune repertoire sequencing. Safety is evaluated according to NCI CTCAE version 5.0.