A Study Evaluating Safety and Efficacy of C-CAR011 in Subjects With B-NHL

Study Overview
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Brief Summary
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This is a single arm, single-center, non-randomized study to evaluate the safety and efficacy of C-CAR011 in relapsed or refractory B cell Non-Hodgkin Lymphoma (NHL).

Detailed Description
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The study will include the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), Treatment and Follow-up.

Official Title
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A Phase 1 Study Evaluating Safety and Efficacy of C-CAR011 in Subjects With B-cell Non-Hodgkin Lymphoma (NHL)

Conditions
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Refractory or Relapsed B-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: C-CAR011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteered to participate in this study and signed informed consent Age 18-70 years old, male or female Relapse or refractory B cell non-Hodgkin's lymphoma 1. Histologically diagnosed as DLBCL (including PMBCL) or follicular lymphoma (grade Ⅲb) according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (2017 Version 1) Progressive disease after the last standard chemotherapy regimens per the IWG Response Criteria (1999) Stable disease after the last standard chemotherapy regimens (at least 4 cycles of first-line therapy or 2 cycles of later-line therapy) per the IWG Response Criteria (1999) Relapse or progressive disease within 12 months after autologous stem cell transplantation (SCT) 2. Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa) At least 2 combination chemotherapy regimens (excluding single agent monoclonal antibody) Relapse or progressive disease within 1 year after last chemotherapy regimens 3. Mantle cell lymphoma Relapse after 1st CR or persistent disease, and not eligible or appropriate for SCT Relapse or progressive disease within 1 year after the last chemotherapy regimens Relapse or progressive disease within 12 months after autologous SCT All subjects must have received anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and anthracycline-containing chemotherapy regimens according to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2017 Version 1) At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm) Expected survival ≥ 12 weeks ECOG score 0-1 Left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography) No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air At least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy) prior to leukapheresis, or at least 4 weeks from monoclonal antibody therapy prior to CAR T cell therapy No contraindications of leukapheresis 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 Exclusion Criteria: History of allergy to cellular products Laboratory tests: absolute neutrophil count < 1.0 × 10^9 /L, platelet count < 50 × 10^9 /L, serum albumin < 30 g/L, serum bilirubin > 1.5 ULN, serum creatinine > ULN, ALT/AST > 3 ULN History of CAR T cell therapy or any other genetically modified T cell therapy Relapse after allogeneic hematopoietic stem cell transplantation Active infections that require treatment (uncomplicated urinary tract infections and bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal treatment are permitted Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as acquired or congenital immune deficiency diseases, including but not limited to HIV infection Class III or IV heart failure according to the NYHA Heart Failure Classifications QT interval prolongation ≥ 450 ms History of epilepsy or other central nervous system disorders Evidence of CNS lymphoma by head enhancement scan or magnetic resonance imaging History of other primary cancers, with the following exceptions Excisional non-melanoma (e.g. cutaneous basal cell carcinoma) Cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer) Autoimmune diseases that require treatment, immune deficiency diseases or other diseases that require immunosuppressive therapy Used of systemic steroids within two weeks (using inhaled steroids is an exception) Women who are pregnant or lactating, or who have breeding intent in 6 months Participated in any other clinical trial within three months Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed

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>Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene | Biological: C-CAR011<br>* Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously at a target dose of 0.5-5.0 x 10^6 anti-CD19 CAR+ T cells/kg<br>* Other names: Anti-CD19 Chimeric Antigen Receptor T cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs) | Vital signs, physical examination, clinical laboratory tests, incidence of adverse events (AEs) and serious adverse events (SAEs) | 12 weeks | 
| Overall response rate (ORR) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) |  | 6 months | 
| Overall response rate (ORR) |  | 12 months | 
| Duration of remission (DOR) |  | 12 months | 
| Progression free survival (PFS) |  | 12 months | 
| Overall survival (OS) |  | 12 months |