Clinical Study of Recombinant Anti-CD19m-CD3 Antibody Injection (A-319) (A-319)

January 19, 2026 updated by: Shanxi Bethune Hospital

Recombinant Anti-CD19m-CD3 Antibody Injection (A-319) for Refractory/Relapsed or MRD-Positive After Induction Chemotherapy Acute B-Cell Lymphoblastic Leukemia (B-ALL) Clinical Study

This is an exploratory study with an open-label, single-arm, single-center design. It plans to enroll subjects with refractory/relapsed acute B-cell lymphoblastic leukemia (B-ALL), or treatment-naive or previously treated B-ALL subjects who achieved complete remission (CR) after induction chemotherapy but still have positive minimal residual disease (MRD). The primary objectives are to preliminarily evaluate the safety, tolerability, pharmacokinetics, biology, preliminary efficacy, and immunogenicity of A-319 subcutaneous injection.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

All of the following criteria must be met for refractory/relapsed acute B-cell lymphoblastic leukemia:

  • 1.Aged 18 to 75 years (inclusive), regardless of gender;
  • 2.Confirmed diagnosis of refractory or relapsed acute B-cell lymphoblastic leukemia (B-ALL) with positive CD19 expression. Definition of refractory or relapsed: failure to respond to conventional induction chemotherapy; early relapse (relapse within 12 months of first remission); relapse after 12 months of first remission with failure to achieve remission following re-induction with the original regimen; second or subsequent relapse, relapse after autologous hematopoietic stem cell transplantation (Auto-HSCT), or relapse after allogeneic hematopoietic stem cell transplantation (Allo-HSCT). (For patients with Philadelphia chromosome-positive [Ph+] disease, they must have received treatment with at least one tyrosine kinase inhibitor [TKI].);
  • 3.Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
  • 4.Bone marrow blast percentage of at least 5% (determined by morphology);
  • 5.Expected life expectancy of at least 3 months;
  • 6.Ability to sign the informed consent form and comply with protocol requirements; if the patient is unable to sign, their legal guardian or representative must sign on their behalf.

All of the following criteria must be met for acute B-cell lymphoblastic leukemia (B-ALL) with positive minimal residual disease (MRD) despite achieving complete remission (CR) via induction chemotherapy:

  • 1.Aged 18 to 75 years (inclusive), regardless of gender;
  • 2.Confirmed diagnosis of acute B-cell lymphoblastic leukemia (B-ALL) with positive CD19 expression;
  • 3.B-ALL that has achieved complete morphological remission (CR) via at least 2 cycles of induction chemotherapy# but remains minimal residual disease (MRD)-positive. MRD positivity is defined as detectable nucleated blast cells ≥ 10-⁴. (For patients with Philadelphia chromosome-positive [Ph+] disease, they must have received treatment with tyrosine kinase inhibitors [TKIs] combined with chemotherapy);
  • 4.Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2;
  • 5.Ability to sign the informed consent form and comply with protocol requirements; if the patient is unable to sign, their legal guardian or representative must sign on their behalf.

Exclusion Criteria:

  • 1.Central nervous system (CNS) leukemia (confirmed by cerebrospinal fluid [CSF] analysis) or acute lymphoblastic leukemia (ALL) with clinically relevant CNS involvement;
  • 2.Burkitt's leukemia, testicular infiltration in acute lymphoblastic leukemia (ALL);
  • 3.A history of malignancy other than ALL within 5 years prior to the initiation of protocol-specific treatment. Exceptions include: malignancies treated with curative intent, with no known active disease for 5 years before enrollment, and deemed by the treating physician to have a low recurrence risk; non-melanoma skin cancer or lentigo maligna that has been adequately treated with no evidence of recurrence; carcinoma in situ of the cervix that has been adequately treated with no evidence of recurrence; ductal carcinoma in situ of the breast that has been adequately treated with no evidence of recurrence;and prostatic intraepithelial neoplasia with no evidence of prostate cancer;
  • 4.Patients with grade 2-4 acute graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), or those with chronic GVHD requiring immunosuppressive therapy;
  • 5.Receipt of autologous hematopoietic stem cell transplantation (Auto-HSCT) within 6 weeks, or allogeneic hematopoietic stem cell transplantation (Allo-HSCT) within 3 months, prior to the start of study drug treatment;
  • 6.Concurrent chemotherapy, radiotherapy, or systemic treatment for GVHD within 2 weeks prior to the start of study drug treatment;
  • 7.Patients with diseases, medical conditions, or social factors that, in the investigator's judgment, may affect study results or compliance. The protocol specifies the following conditions that disqualify patients from participating in the study: uncontrolled acute infection or confirmed bacteremia; known human immunodeficiency virus (HIV) infection, or acute hepatitis B or hepatitis C; patients with severe dyspnea, impaired pulmonary function, or requiring continuous oxygen supplementation; New York Heart Association (NYHA) heart failure classification of grade 3 or 4; myocardial infarction, unstable angina, stroke, transient ischemic attack, severe arrhythmia, or uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg) within 6 months prior to drug administration;
  • 8.Laboratory test requirements are as follows: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), or > 5 × ULN if liver metastasis is present; total bilirubin > 1.5 × ULN;creatinine clearance < 50 mL/min (calculated using the Cockroft-Gault formula); coagulation function: International Normalized Ratio (INR) > 1.6 (unless on anticoagulant therapy);for patients on oral anticoagulant therapy with a stable dose (for at least 14 days) (e.g., warfarin), INR must be ≤ 3.0 with no bleeding tendency (i.e., no bleeding within 14 days prior to the first dose of the study drug); use of low-molecular-weight heparin is permitted for subjects;
  • 9.Previous receipt of anti-CD19 therapy (including CAR-T cell therapy), or immunotherapy (e.g., rituximab) within 4 weeks prior to A-319 treatment;
  • 10:Presence of adverse events (except alopecia) caused by anti-tumor treatment that have not resolved to grade 1;
  • 11.Pregnant women (positive pregnancy test), lactating women, or women of childbearing potential who refuse to use contraception from the time of signing the informed consent form until at least 3 months after the end of the study; women of childbearing potential must have a positive pregnancy test (human chorionic gonadotropin [HCG] test) within 7 days prior to Day 1 of treatment;
  • 12.Male patients (except those who have undergone surgical sterilization) who refuse to use contraception from the time of signing the informed consent form until at least 3 months after the end of the study;
  • 13.Known hypersensitivity to the study drug or its excipients;
  • 14.Patients deemed unsuitable for participation in this study by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 1.8 μg/kg dose group
The maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, a treatment dose of 1.8 μg/kg will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.
Drug: Treatment with A319
The maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, the corresponding treatment dose will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.
Experimental: 3.6 μg/kg dose group
The maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, a treatment dose of 3.6 μg/kg will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.
Drug: Treatment with A319
The maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, the corresponding treatment dose will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.
Experimental: 5.0 μg/kg dose group
The maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, a treatment dose of 5.0 μg/kg will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.
Drug: Treatment with A319
The maximum duration of treatment is no more than 4 cycles (one cycle is defined as: 1 week of induction + 3 weeks of treatment + 2 weeks of drug withdrawal). During the 1st week, induction doses of 0.15 μg/kg, 0.45 μg/kg, and 0.9 μg/kg will be administered subcutaneously on Days 1, 3, and 5 respectively. From Weeks 2 to 4, the corresponding treatment dose will be administered subcutaneously on Days 1, 3, and 5 of each week. Weeks 5 to 6 will be the drug withdrawal period.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety Analysis
Time Frame: From the signing of the informed consent form to 30 days after the last dose
Safety will be evaluated based on the incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
From the signing of the informed consent form to 30 days after the last dose
Characteristics of Dose-Limiting Toxicity (DLT)
Time Frame: During the first cycle (each cycle lasts 42 days)
Dose Limiting Toxicity (DLT) is defined as the occurrence of Grade 3 or higher non-hematologic toxicity (including neurotoxicity) during the first cycle (4 weeks of treatment plus 2 weeks of treatment holiday).
During the first cycle (each cycle lasts 42 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Peripheral Blood Lymphocyte Count
Time Frame: No more than 4 cycles (each cycle is 42 days)
Pharmacodynamic endpoints:Detection of CD20+, CD19+, CD3+ T cells, CD4+ T cells, and CD8+ T cells.
No more than 4 cycles (each cycle is 42 days)
Maximum Concentration (Cmax)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Mean
Time Frame: During the first cycle (each cycle lasts 42 days)
It will be evaluated based on the levels of cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, IFNγ, TNFα, IL-1β) in peripheral blood.
During the first cycle (each cycle lasts 42 days)
Best response rate
Time Frame: No more than 4 cycles (each cycle is 42 days)
Hematologic Complete Remission (CR) or Hematologic Complete Remission with Incomplete Hematologic Recovery (CRi)
No more than 4 cycles (each cycle is 42 days)
Minimal Residual Disease (MRD) Response Rate
Time Frame: No more than 4 cycles (each cycle is 42 days)
No more than 4 cycles (each cycle is 42 days)
Time to Hematologic Relapse
Time Frame: 4 cycles (each cycle is 42 days) plus a 12-month survival follow-up period
Duration of Response, DOR
4 cycles (each cycle is 42 days) plus a 12-month survival follow-up period
Relapse-Free Survival (RFS)
Time Frame: Within 2 years
Within 2 years
Overall Survival (OS)
Time Frame: Within 2 years
Within 2 years
Percentage of subjects who undergo allogeneic hematopoietic stem cell transplantation (Allo-HSCT) after achieving complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or minimal residual disease (MRD) negativity followi
Time Frame: Within 2 years
Within 2 years
Immunogenicity
Time Frame: No more than 4 cycles (each cycle is 42 days)
Number and percentage of subjects who develop anti-A-319 antibodies (ADA)
No more than 4 cycles (each cycle is 42 days)
Time to Maximum Concentration (Tmax)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Area Under the Concentration-Time Curve (AUC)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Mean Residence Time (MRT)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Apparent Volume of Distribution (Vd)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Total Clearance (CL/F)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Volume of Distribution (Vz/F)
Time Frame: During the first cycle (each cycle lasts 42 days)
Pharmacokinetic endpoints
During the first cycle (each cycle lasts 42 days)
Standard Deviation (SD)
Time Frame: During the first cycle (each cycle lasts 42 days)
Detection of biomarkers (serum cytokines): Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Tumor Necrosis Factor-α (TNF-α), Interferon-γ (IFN-γ), and Interleukin-1β (IL-1β)
During the first cycle (each cycle lasts 42 days)
Coefficient of Variation (CV)
Time Frame: During the first cycle (each cycle lasts 42 days)
Detection of biomarkers (serum cytokines): Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-10 (IL-10), Tumor Necrosis Factor-α (TNF-α), Interferon-γ (IFN-γ), and Interleukin-1β (IL-1β)
During the first cycle (each cycle lasts 42 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shanxi Bethune Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 2, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 28, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IM-2025-06

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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