Immuno-Targeted Therapy Plus Low-Dose Chemotherapy for Newly Diagnosed Adult Ph-Negative B-ALL: A Prospective Umbrella Trial

A Prospective Umbrella Clinical Trial of Immuno-Targeted Agents Combined With Low-Dose Chemotherapy for Newly Diagnosed Adult Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

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.

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.