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

NCT07643103 | Not Yet Recruiting Phase 2

• 2 other identifiers: IIT2026063IIT2026063-EC-1
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief 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)

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (8)

• Next-Generation Sequencing (NGS)-MRD Negative Remission Rate

  Within 3 months after treatment initiation

• Best MRD Clearance Rate

  Within 3 months after treatment initiation

• Overall Survival (OS)

  Up to 5 years

• Disease-Free Survival (DFS)

  Up to 5 years

• Relapse-Free Survival (RFS)

  Up to 5 years

Study Arms (1)

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.

Drug: Inotuzumab Ozogamicin (IO); Drug: Venetoclax; Drug: Blinatumomab; Biological: CD19-directed chimeric antigen receptor (CAR-T) T cells; Drug: Vincristine; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine (Ara-C); Drug: Prednisone; Drug: Mercaptopurine 50 mg

Interventions

Blinatumomab DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Inotuzumab Ozogamicin (IO) DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

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.

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Prednisone DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Venetoclax DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

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

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Vincristine DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Cyclophosphamide DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Dexamethasone DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Methotrexate DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Mercaptopurine 50 mg DRUG

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

Immuno-Targeted Therapy Plus Low-Dose Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

MeSH Terms

Interventions

Inotuzumab Ozogamicin; venetoclax; blinatumomab; Vincristine; Cyclophosphamide; Dexamethasone; Methotrexate; Cytarabine; Prednisone; Mercaptopurine

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienediols; Sulfhydryl Compounds; Sulfur Compounds; Purines

Central Study Contacts

Ying Wang, MD, PhD

CONTACT

+86 22-23608095; wangying1@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 11, 2026
• Study Start: June 12, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2030
• Last Updated: June 11, 2026

Record last verified: 2026-06