Study Summary
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.
Interventions
Inotuzumab Ozogamicin (IO)DRUG
Anti-CD22 antibody-drug conjugate (ADC) administered intravenously during induction and consolidation therapy.
VenetoclaxDRUG
BCL-2 inhibitor administered orally daily during induction and consolidation cycles to enhance leukemic cell apoptosis.
BlinatumomabDRUG
CD19/CD3 bispecific T-cell engager (BiTE) administered as continuous intravenous infusion during consolidation therapy.
CD19-directed chimeric antigen receptor (CAR-T) T cellsBIOLOGICAL
Autologous CD19 CAR-T cell therapy administered as a single intravenous infusion as optional consolidation therapy for eligible patients.
VincristineDRUG
A vinca alkaloid that inhibits microtubule formation by binding to tubulin, resulting in mitotic arrest and inhibition of proliferation of rapidly dividing leukemic cells.
CyclophosphamideDRUG
An alkylating agent that forms DNA cross-links, leading to inhibition of DNA replication and transcription and subsequent apoptosis of rapidly proliferating hematopoietic cells.
DexamethasoneDRUG
A synthetic glucocorticoid that induces lymphoid cell apoptosis and exerts anti-inflammatory and immunosuppressive effects, contributing to reduction of leukemic burden.
MethotrexateDRUG
A folate antimetabolite that inhibits dihydrofolate reductase, resulting in impaired DNA synthesis and cell replication, particularly in rapidly dividing lymphoid cells.
Cytarabine (Ara-C)DRUG
A pyrimidine nucleoside analog that inhibits DNA polymerase, leading to termination of DNA chain elongation and inhibition of leukemic cell proliferation.
PrednisoneDRUG
A glucocorticoid that induces apoptosis in lymphoid cells and provides anti-inflammatory and immunosuppressive effects as part of multi-agent leukemia therapy.
Mercaptopurine 50 mgDRUG
A purine analog antimetabolite that interferes with purine nucleotide synthesis and incorporates into DNA and RNA, inhibiting nucleic acid synthesis and cell proliferation.