Study of A-319 in Patients With Relapsed or Refractory B-cell Lymphoma

Study Overview
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Brief Summary
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Title: A Phase I, Single Centre, Open-label, Dose-escalation Study of A-319 in Patients With Relapsed or Refractory B-cell Lymphoma

Detailed Description
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Protocol Number: SP071744 Study Stage: Phase I Study Number: 1 site Subject Number: up to 54 patients with Relapsed or Refractory B-cell Lymphoma

Official Title
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A Phase I, Single Centre, Open-label, Dose-escalation Study of A-319 in Patients With Relapsed or Refractory B-cell Lymphoma

Conditions
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Relapsed or Refractory B-cell Lymphoma

Intervention / Treatment
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* Biological: Recombinant Anti-CD19m-CD3 Antibody Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years, all genders Patients with definite B-cell Lymphoma, includes FL, MZL, MCL, DLBCL. Patients With Relapsed or Refractory B-cell Lymphoma ECOG ≤ 2 Lesions are measurable in 21 days before treatment Normal bone marrow function Normal liver, kidney, lung and heart function the Subjects can sign the ICF and obey the protocol, elsewise, his/her guardian should sign Life expectancy is at least 3 months Exclusion Criteria:• Past or present CNS disease Associated with lymphoma by the infiltrates of CNS A history of autoimmune disease with CNS involvement or autoimmune disease Previous history of autoimmune disease or other malignancy A history of deep venous thrombosis or pulmonary embolism Auto-HSCT was performed within 12 weeks prior to initiation of treatment Previous organ transplantation or allogeneic hematopoietic stem cell transplantation The Investigator determined that the patients were associated with a disease, medical condition, or social factor that might affect study results or compliance Immunosuppressant are being used Radiotherapy was given within 6 weeks prior to A-319 treatment Chemotherapy, immunotherapy and targeted therapy were received within 4 weeks before A-319 treatment Previous CAR-T cell therapy Received anti-lymphoma drugs in the first 4 weeks of A-319 treatment There was no recovery of toxic effects (CTCAE> grade 1 adverse events) at the last treatment, except hair loss Those who underwent major surgery 28 days before enrollment (excluding lymph node biopsy);Or plan to operate during the study period Those who had received active/attenuated live vaccine within 28 days prior to screening For pregnant (positive pregnancy test) and lactating women, those of childbearing age who signed the informed consent form and did not agree to use contraception for at least 3 months after the end of the study;Within 7 days prior to the first day of treatment, women of childbearing age require a positive serum pregnancy test (HCG) Male patients who signed informed consent forms and did not agree to use contraception for at least 3 months at the end of the study (except surgical sterilization) Known allergy to immunoglobulin or research drugs and their excipients Patients considered unfit to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br>A-319 dosage: 0.05, 0.15, 0.03, 0.06, 0.12, 0.18, 0.24 μg/kg | Biological: Recombinant Anti-CD19m-CD3 Antibody Injection<br>* Intravenous Infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Incidence and Characteristics of SAE of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | Incidence and Characteristics of SAE | At the end of Cycle 1 (each cycle is 28 days) | 
| Evaluate the MTD and DLT of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | dose limited toxicity(DLT), maximum tolerance dose(MTD) | At the end of Cycle 1 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the PK(Cmax) of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | Peak Plasma Concentration(Cmax) | At the end of Cycle3 (each cycle is 28 days) | 
| Evaluate the PK(AUC) of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | Area under the plasma concentration versus time curve(AUC) | At the end of Cycle3 (each cycle is 28 days) | 
| Evaluate the PK(Tmax) of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | time to peak (Tmax) | At the end of Cycle3 (each cycle is 28 days) | 
| Evaluate the PK(T1/2) of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | half-life time(T1/2) | At the end of Cycle3 (each cycle is 28 days) | 
| Evaluate the PK(CL) of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | clearance(CL) | At the end of Cycle3 (each cycle is 28 days) | 
| Evaluate the PK(Vz) of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | volume of distribution(Vz) | At the end of Cycle3 (each cycle is 28 days) | 
| Evaluate the PD of A-319 Treat on Relapsed or Refractory B-cell Lymphoma | B-cell level | At the end of Cycle3 (each cycle is 28 days) |