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

Official title

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

Overview

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

• 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.

Primary outcome measures

• Flow Cytometric MRD-Negative Complete Remission Rate [Time frame: At the end of induction therapy (approximately 1 month after treatment initiation)]

Secondary outcome measures (8)

• Next-Generation Sequencing (NGS)-MRD Negative Remission Rate [Time frame: Within 3 months after treatment initiation]
• Best MRD Clearance Rate [Time frame: Within 3 months after treatment initiation]
• Overall Survival (OS) [Time frame: Up to 5 years]
• Disease-Free Survival (DFS) [Time frame: Up to 5 years]
• Relapse-Free Survival (RFS) [Time frame: Up to 5 years]
• 30-Day Mortality [Time frame: 30 days]
• 60-Day Mortality [Time frame: 60 days]
• Incidence of Adverse Events [Time frame: From treatment initiation through completion of study treatment, up to 5 years]

Eligibility criteria

Inclusion criteria

• Newly diagnosed adult (≥18 years) patients with Ph-negative B-cell acute lymphoblastic leukemia according to WHO 2022 criteria.
• CD22-positive expression on tumor cells (CD22 ≥20%).
• Expected survival ≥3 months.
• Sexually active men and women of childbearing potential must agree to use effective contraception.
• 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

• Burkitt lymphoma/leukemia.
• Acute leukemia of ambiguous lineage.
• Pregnant women.
• Severe, uncontrolled active infections.
• History of chronic liver disease (e.g., liver cirrhosis) or prior veno-occlusive disease (VOD) / sinusoidal obstruction syndrome (SOS).
• 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.
• Uncontrolled active hepatitis B or hepatitis C infection, or known HIV seropositivity. HIV testing may be required according to local regulations or standards.
• Psychiatric disorders that may impair the subject's ability to complete treatment or provide informed consent.
• Any other conditions deemed by the investigator to render the subject unsuitable for participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07643103 · IIT2026063 · IIT2026063-EC-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗