A Study of C-CAR066 in Subjects With r/r Diffuse Large B Cell Lymphoma Who Received CD19 CAR-T Therapy

Study Overview
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Brief Summary
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This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of C-CAR066 in treatment of r/r DLBCL who received CD19 CAR-T therapy.

Detailed Description
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This study plans to enroll 10 patients to assess the safety and efficacy of C-CAR066. Subjects who meet the eligibility criteria will receive a single dose of C-CAR066 injection. The study will include the following sequential phases: Screening, Pre-Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR066 infusion and Follow-up Visit.

Official Title
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A Study Evaluating Safety and Efficacy of CBM.CD20 CAR-T(C-CAR066) in Subjects With r/r Diffuse Large B Cell Lymphoma Who Received CD19 CAR-T Therapy

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: C-CAR066


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient volunteered to participate in the study, and signed the Informed Consent Age 18-75 years old, male or female Patients diagnosed with diffuse large B-cell lymphoma (DLBCL, De novo or transformed) histologically according to the 2016 WHO Classification, at least one measurable lesion(LDi≥1.5 cm) r/r DLBCL patients who received prior CD19 CAR-T therapy, and positive for CD20 At least 2 weeks from last treatment (radiation, chemotherapy, mAb, etc) to apheresis Adequate organ and bone marrow fuction No contraindications of apheresis Expected survival time > 3 months ECOG scores 0 - 1 Exclusion Criteria: Have a history of allergy to cellular products Patients with cardiac insufficiency classified as Class III or IV according to the New York Heart Association (NYHA) Heart Function Classification Standard A history of craniocerebral trauma, consciousness disorder, epilepsy, cerebral ischemia or hemorrhagic cerebrovascular disease Patients with active CNS involvement Patients with autoimmune disease, immunodeficiency, or other treatment requiring inhibitors Severe active infection (except simple urinary tract, bacterial pharyngitis), or currently receiving intravenous antibiotics. However, prophylactic antibiotics, antiviral and antifungal treatments are allowed Live vaccination within 4 weeks before peripheral blood apheresis HIV, HBV, HCV and TPPA / RPR infections, and HBV carriers Have a history of alcoholism, drug addiction and mental illness Non-sterile subjects had any of the following: a) being pregnant / lactating; or b) having a pregnancy plan during the trial; or c) having fertility without taking effective contraception Patients with severe fludarabine or cyclophosphamide hypersensitivity The patient has a history of other primary cancers, except for the following: Non-melanoma such as skin basal cell carcinoma cured by resection Cured carcinoma in situ such as cervical, bladder or breast cancer The investigators believe that there are other circumstances that are not suitable for the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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-CAR066<br>Autologous C-CAR066 (CD20-directed CAR T-cell) administered by intravenous (IV) infusion | Drug: C-CAR066<br>* Autologous 2nd generation CD20-directed CAR-T cells, single infusion intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events | The incidence of treatment-emergent adverse events (TEAEs) | Up to 12 weeks after C-CAR066 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The percentage of subjects who achieved complete response and partial response | Up to 24 months after C-CAR066 infusion | 
| Complete response rate (CRR) | The percentage of subjects who achieved complete response | Up to 24 months after C-CAR066 infusion | 
| Duration of response (DOR) | The time from the date of first response (PR or CR) to the date of disease progression or death after C-CAR066 infusion | Up to 24 months after C-CAR066 infusion | 
| Progression free survival (PFS) | The time from C-CAR066 infusion to the date of progression as assessed by Lugano 2014 criteria or death | Up to 24 months after C-CAR066 infusion | 
| Overall survival (OS) | Time from C-CAR066 infusion to death from any cause | Up to 24 months after C-CAR066 infusion |