Assessment of Safety and Efficacy of IM19 for Relapsed or Refractory NHL Patients

Study Overview
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Brief Summary
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n this study, approximately 30 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were recruited for a single reinfusion of IM19-CD28 and IM19-41BB CAR-T cells. Assess the safety, tolerability of treatment, and initially observe the efficacy.

Detailed Description
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Dose-escalation:Patients entered the IM19-41BB or IM19-CD28 group and performed dose escalation studies in three dose groups. According to the results of the previous dose escalation study, select one dose to continue the enrollment of 6 patients for extended studies.

Official Title
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Clinical Study to Evaluate the Safety and Efficacy of IM19 CAR-T Cell Therapy in Patients With Relapsed or Refractory CD19-positive Non-Hodgkin's Lymphoma

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Biological: IM19
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Relapsed or refractory CD19-positive non-Hodgkin lymphoma (NHL) patients. 1 Diffuse large B lymphoma (DLBCL), follicular lymphoma (FL), primary mediastinal B-cell lymphoma (PMBCL) patients meet one of the following conditions: I Patients who have relapsed or are refractory after at least 2 previous treatments; II Patients who have relapsed after transplantation. 2 Patients with relapsed or refractory mantle cell lymphoma after at least one treatment. Patients must have evaluable disease evidence; Age ≥ 18 years old; The expected life span is more than 3 months; ECOG score 0-2 points (see Attachment 2); Women of childbearing age have a negative blood pregnancy test before the start of the trial and agree to have effective contraceptive measures during the trial until the last follow-up; Those who voluntarily participate in the trial and sign the informed consent. Exclusion criteria: Patients with high-risk organ involvement: tumors invade one of the central nervous system, gastrointestinal tract, lungs, pericardium, and large vessels; Those who have a graft-versus-host response and need to use immunosuppressive drugs; or who have a disease of the autoimmune system; Use chemotherapy or radiotherapy within 3 days before the blood collection period; Those who have used systemic steroids within the 5 days prior to the blood sampling period (except recently or currently using inhaled steroids); Use stimulating bone marrow hematopoietic cells to produce drugs (whitening needles, etc.) within 5 days before the blood collection period; Those who have previously used any gene therapy products; History of epilepsy or other diseases of the central nervous system; New York Heart Association (NYHA) class III or above (see Annex 3); creatinine> 1.5 times the upper limit of normal or ALT / AST> 3 times the upper limit of normal or bilirubin> 2 times the normal upper limit; active Hepatitis B or Hepatitis C virus, HIV or other untreated active infections; pregnant or lactating women; suffer from other uncontrolled diseases that the researcher considers inappropriate; Any condition that the investigator believes may increase the subject's risk or interfere with the test results.

Ages Eligible for Study
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Minimum Age: 18 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: IM19 CAR-T cells<br>3*10^5/kg，1*10^6/kg，3*10^6/kg IM19 CAR-T cell.Two days before cell infusion, all patients will be treated with fludarabine and Cyclophosphamide for 3 days | Biological: IM19<br>* CAR-T cells<br>Drug: Fludarabine<br>* Two days before cell infusion, all patients will be treated with fludarabine for 3 days<br>Drug: Cyclophosphamide<br>* Two days before cell infusion, all patients will be treated with Cyclophosphamide for 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of study related adverse events | >= Grade 3 signs/symptoms,laboratory toxicities,and clinical events that are possibly,likely,or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | (1) a morphologic complete response (CR) or (2) a complete response with incomplete recovery of counts (CRi) (based on NCCN guidelines (National Comprehensive Cancer Network (NCCN), 2014) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T