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

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 therapy 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 Ⅰb Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Conditions
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B-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: CD19-directed CAR-T cells


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 ,Histologically diagnosed as DLBCL,follicular lymphoma and Mantle cell lymphoma according to the NCCN. nonHodgkin's lymphoma Clinical Practice Guidelines (2017 Version 1) DLBCL and Follicular Lymphoma (stage Ⅲ-Ⅳ, grade Ⅲb). Progressive disease after the last standard chemotherapy regimens. Stable disease after the last standard chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later-line therapy). Relapse or progressive disease within 12 months after autologous stem cell transplantation (SCT). Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa) Relapse or progressive disease within 1 year after the last standard chemotherapy regimens(At least 2 combination chemotherapy regimens). Stable disease after the last standard chemotherapy regimens(at least 2 cycles of combination chemotherapy regimens). 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(at least 4 cycles of first-line therapy or 2 cycles of later- line therapy). 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 ≥ 1.5cm). 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. 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: CD19-directed CAR-T cells<br>Lymphocytes will be transduced with lentiviral vector containing CAR-CD19 gene | Biological: CD19-directed CAR-T cells<br>* 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 cells (C- CAR011);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AE | Incidence of adverse events (AEs) and serious adverse events (SAEs) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | The ORR will be assessed at weeks 4 ，weeks 12 ，months 6 and months 12 | 12 months | 
| Duration of remission (DOR) | The DOR will be assessed at months 12 | 12 months | 
| Progression free survival (PFS) | The PFS will be assessed at months 12 | 12 months | 
| Overall survival rate（OSR） | The OSR will be assessed at weeks 12 ，months 6 and months 12 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-cell Non-Hodgkin Lymphoma, Refractory, Relapsed