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

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.

Conditions

• Ph- Acute Lymphoblastic Leukemia (Ph-ALL)

Interventions

DRUG

Inotuzumab Ozogamicin (IO)

Anti-CD22 antibody-drug conjugate (ADC) administered intravenously during induction and consolidation therapy.

DRUG

Venetoclax

BCL-2 inhibitor administered orally daily during induction and consolidation cycles to enhance leukemic cell apoptosis.

DRUG

Blinatumomab

CD19/CD3 bispecific T-cell engager (BiTE) administered as continuous intravenous infusion during consolidation therapy.

BIOLOGICAL

CD19-directed chimeric antigen receptor (CAR-T) T cells

Autologous CD19 CAR-T cell therapy administered as a single intravenous infusion as optional consolidation therapy for eligible patients.

DRUG

Vincristine

A vinca alkaloid that inhibits microtubule formation by binding to tubulin, resulting in mitotic arrest and inhibition of proliferation of rapidly dividing leukemic cells.

DRUG

Cyclophosphamide

An alkylating agent that forms DNA cross-links, leading to inhibition of DNA replication and transcription and subsequent apoptosis of rapidly proliferating hematopoietic cells.

DRUG

Dexamethasone

A synthetic glucocorticoid that induces lymphoid cell apoptosis and exerts anti-inflammatory and immunosuppressive effects, contributing to reduction of leukemic burden.

DRUG

Methotrexate

A folate antimetabolite that inhibits dihydrofolate reductase, resulting in impaired DNA synthesis and cell replication, particularly in rapidly dividing lymphoid cells.

DRUG

Cytarabine (Ara-C)

A pyrimidine nucleoside analog that inhibits DNA polymerase, leading to termination of DNA chain elongation and inhibition of leukemic cell proliferation.

DRUG

Prednisone

A glucocorticoid that induces apoptosis in lymphoid cells and provides anti-inflammatory and immunosuppressive effects as part of multi-agent leukemia therapy.

DRUG

Mercaptopurine 50 mg

A purine analog antimetabolite that interferes with purine nucleotide synthesis and incorporates into DNA and RNA, inhibiting nucleic acid synthesis and cell proliferation.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-12

Primary Completion

2028-05-31

Completion

2030-05-31