Immuno-Targeted Therapy Plus Low-Dose Chemotherapy for Newly Diagnosed Adult Ph-Negative B-ALL: A Prospective Umbrella Trial (Ph- ALL-2026)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ph- Acute Lymphoblastic Leukemia (Ph-ALL)
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Wang, MD, PhD; Phone Number: +86 22-23608095; Email: wangying1@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Immuno-Targeted Therapy Plus Low-Dose Chemotherapy; 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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Next-Generation Sequencing (NGS)-MRD Negative Remission Rate	Proportion of patients achieving MRD-negative remission assessed by immune repertoire sequencing.	Within 3 months after treatment initiation
Best MRD Clearance Rate	Proportion of patients achieving the deepest MRD response during the first 3 months of treatment as assessed by flow cytometry, quantitative PCR, or immune repertoire sequencing.	Within 3 months after treatment initiation
Overall Survival (OS)	Time from study enrollment to death from any cause.	Up to 5 years
Disease-Free Survival (DFS)	Time from achievement of complete remission to relapse or death from any cause.	Up to 5 years
Relapse-Free Survival (RFS)	Time from achievement of MRD-negative remission to hematologic relapse or death.	Up to 5 years
30-Day Mortality	Proportion of patients who die from any cause within 30 days after treatment initiation.	30 days
60-Day Mortality	Proportion of patients who die from any cause within 60 days after treatment initiation.	60 days
Incidence of Adverse Events	Frequency, severity, and type of adverse events graded according to the National Cancer	From treatment initiation through completion of study treatment, up to 5 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Estimated): June 12, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Carbohydrates; Alkaloids; Polycyclic Compounds; Glycosides; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Purines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Pterins; Pteridines; Pregnadienetriols; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Arabinonucleosides; Aminopterin; Aminoglycosides; Sulfhydryl Compounds; Calicheamicins; Inotuzumab Ozogamicin; Dexamethasone; Methotrexate; Prednisone; Cyclophosphamide; Cytarabine; Vincristine; Mercaptopurine; venetoclax; blinatumomab
• Other Study ID Numbers: IIT2026063; IIT2026063-EC-1 (Other Identifier: Ethics Committee of Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No