A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 Treatment in DLBCL Subjects

Study Overview
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Brief Summary
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The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR011 in treatment of refractory DLBCL

Detailed Description
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The 3x3 dose escalation design will be adopted in order to determine the maximum tolerated dose (MTD). Subjects will be enrolled into low-dose group, medium-dose group and high-dose group as below: Dose CAR+ cells/kg Low 0.8×106 Medium 2.5×106 High 5.0×106 DLT is evaluated within 30 days post C-CAR011 infusion).

Official Title
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A Phase 1 Single Center, Non-randomized Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Refractory Diffuse Large B-cell Lymphoma

Conditions
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Refractory Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Biological: C-CAR-011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (3rd edition 2016) Refractory DLBCL All subjects must have received adequate prior therapy including anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2016 Version 3) At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm) Age 18-70 years old, male or female Expected survival ≥ 12 weeks ECOG score 0-1 Subject's left ventricular ejection fraction (LVEF) is ≥ 50% and no evidence of pericardial effusion as determined by an ECHO At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments) No contraindications of peripheral blood apheresis Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial measures Volunteered to participate in this study and signed informed consent Exclusion Criteria: Have a history of allergy to cellular products Used any genetically modified T cell therapy History of allogeneic hematopoietic stem cell transplantation Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis allowed) or currently receiving intravenous antibiotic therapy and received intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons Patients with class III and IV heart failure according to the NYHA Heart Failure Classifications A history of QT prolongation A history of epilepsy or other central nervous system disorders The patient had a history of other primary cancers, with the following exceptions: Excisional non-melanoma such as cutaneous basal cell carcinoma; Cured in situ carcinoma such as cervical cancer, bladder cancer or breast cancer Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy Used of systemic steroids within two weeks (using inhaled steroids is an exception) Women who are pregnant or lactating or have breeding intent in 6 months Participated in any other clinical trial within three months The investigators believe that any increase in the risk of the subject or interference with the results of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: C-CAR011<br>C-CAR011 infusion In the first cell therapy 0, 1 and 2 days, respectively 10%, 30% and 60% ratio three times reinfusion. | Biological: C-CAR-011<br>* lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene.<br>* Other names: CAR-CD19;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of C-CAR011 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 4 and weeks 12 according to International Working Group (IWG) revised criteria. | 4 and 12 weeks | 
| Disease control rate | Disease control rate (DCR） = complete response (CR) rate + partial response (PR) rate + stable disease (SD) rate, DCR will be assessed at weeks 12 according to International Working Group (IWG) revised criteria. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory diffuse large B-cell lymphoma, anti-CD19 chimeric antigen receptor T-cell