Safety, Tolerability, and Efficacy of AT101 in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Determine MTD based on the safety and tolerability of AT101 and the RP2D for patients with recurrent or non-reactive B-cell NHL.

Detailed Description
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Determine the maximum tolerant dose (MTD) based on the safety and tolerability of AT101 and the recommended dose 2 dose (RP2D) in phase 2 trials for patients with recurrent or non-reactive B cell non-Hodgkin lymphoma (B-cell NHL).

Official Title
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An Open-label, Single-arm, Multi-center, Phase I/II Study to Evaluate the Safety, Tolerability, and Efficacy of AT101 (Anti-CD19 Chimeric Antigen Receptor T Cell) in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Conditions
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B-cell Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: AT101(Anti-CD19 Chimeric Antigen Receptor T cell)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: B cell non-Hodgkin lymphoma based on WHO classification 2017 incompatible with existing standard therapies or have had disease progression, and whose standard therapies do not currently have available standard therapies due to reasons such as intolerance/inadequacies or rejection The Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 adequate hematological, kidney, liver, lung, heart and bone marrow function without blood transfusion within two weeks prior to screening Those with a minimum life expectancy of 12 weeks or more In women with childbearing, clinical response tests (serum- or ure-hCG) were negatively identified during this trial Those who have agreed in writing to participate voluntarily in this trial Exclusion Criteria: Those who have previously had a history of treating homologic autologous hemoblastitis (allogeneic HSCT) At101/adcidmilisers, anticancer chemotherapy/adcidms for lymphodeletion or those who are hypersensitive to tocilizumab Those who cannot take autologous blood Those who have received chemotherapy or radiotherapy, excluding lymphodeletion, within two weeks prior to IP administration Persons who have not been recovered (CTCAE grade ≤1 or baseline) due to previous treatment Those who have identified a condition that, at the test's discretion, may affect safety and validation during the trial period. Those who have identified the following forces at the time of screening: Those who have been clinically aware of heart disease within 6 months prior to screening Those identified as thromboembolic disease, pulmonary embolism or bleeding bleeding diatheses within 6 months prior to screening Those who have identified a history of malignant tumors other than B-cell non-Hodgkin's lymphoma within five years prior to screening Those who have undergone major surgery within 4 weeks prior to screening Those who have undergone non-critical surgery within two weeks prior to screening Childbearing women or men who do not have the will to use effective contraception for a longer period of time, either 12 months after clinical trial period and AT101 administration or when AT101 in the body is not identified Those who have been administered or applied to other IP/ID within 4 weeks of screening Those who are addicted to alcohol and/or medication Those who are unfit or unable to participate in this trial when judged by PI

Ages Eligible for Study
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Minimum Age: 19 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: AT101(Anti-CD19 Chimeric Antigen Receptor T cell)<br>Anti-CD19 Chimeric Antigen Receptor T cell | Drug: AT101(Anti-CD19 Chimeric Antigen Receptor T cell)<br>* Anti-CD19 Chimeric Antigen Receptor T cell<br>* Other names: AT101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerant dose (MTD) and Recommended Phase 2 Dose (RP2D) | Phase I: Tolerability of AT101 and the recommended dose 2 dose (RP2D) in phase 2 trials | 28 days | 
| Overall response rate (ORR) by Independent assessment | Phase II: Proportion of subjects whose best overall response in tumor evaluation was evaluated as a complete response or a partial response | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) by Investigator assessment | Proportion of subjects whose best overall response in tumor evaluation | 5 years | 
| Duration of overall response (DOR) | Time from first response (CR or PR) to the date of initial objectively documented progression | 5 years | 
| Overall survival(OS) | Time from randomization to death | 5 years | 
| Progression free survival (PFS) | Time from randomization to disease progression or death | 5 years | 
| Time to response (TTR) | Time from randomization to CR or PR | 5 years | 
| Event free survival (EFS) | Time from randomization to progression, subsequent chemotherapy or death | 5 years | 
| Incidence of adverse Event |  | 5 years | 
| Peak concentration (Cmax) of AT101 |  | 5 years | 
| Area under the concentration versus time curve (AUC) of AT101 |  | 5 years | 
| AT101 transgene expression |  | 5 years | 
| Replication-competent lentivirus (RCL) as Assessed by quantitative polymerase |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anti-CD19 Chimeric Antigen Receptor T cell