Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B-NHL After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

Study Overview
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Brief Summary
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This is a phase I, single center study to assess the efficacy and safety of ThisCART19A in adult with Non-Hodgkins Lymphoma in China.

Official Title
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Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cells Non-Hodgkin's Lymphoma(B-NHL) After Failure of Autologous CAR-T Therapy

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Biological: ThisCART19A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cellular or histopathological diagnosis of B-cell non-Hodgkin's lymphoma (B-NHL) includes: diffuse Large B-cell lymphoma (DLBCL), follicular lymphoma to DLBCL (tFL), follicular lymphatic (FL), Mantle cell lymphoma (MCL), primary Mediastinal Large B-cell lymphoma (PMBCL), etc. Failing to autologous CAR-T therapy. At least one available lesion to be assessed. Good organ function during screening. Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before. Exclusion Criteria: Allergic to preconditioning measures. Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited. Uncontrollable bacterial, fungal and viral infection during screening. Patients had pulmonary embolism within 3 months prior to enrollment. Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment. Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment. Had big lesion(single lesion diameter ≥10 cm). Bone marrow involvement≥5%. Receive allogeneic hematopoietic stem cell transplantation less than 100 days. Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) . Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion. Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ThisCART19A 2×10^6 cells/kg for dose level 1<br>Patients will receive 2×10^6 cells/kg of ThisCART19A | Biological: ThisCART19A<br>* each patient will receive a dose level per body weight(kg) for only once.<br>|
| Experimental: ThisCART19A 3×10^6 cells/kg as dose level 2<br>Patients will receive 3×10^6 cells/kg of ThisCART19A | Biological: ThisCART19A<br>* each patient will receive a dose level per body weight(kg) for only once.<br>|
| Experimental: Patients will receive 4×10^6 cells/kg as dose level 3<br>Patients will receive 4×10^6 cells/kg of ThisCART19A | Biological: ThisCART19A<br>* each patient will receive a dose level per body weight(kg) for only once.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage | DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level. | 28 days | 
| Objective Response Rate in patient with NHL during dose expansion stage | the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate during dose escalation stage and expansion stage | the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment | 12 months | 
| Duration of response(DOR) during dose escalation stage and expansion stage | The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) | 12 months | 
| OS(overall survival) during dose escalation stage and expansion stage | Overall survival (OS) is defined as the time from the date of lymphodepletion until death from any cause. | 12 months | 
| Time to remission(TTR) during dose escalation stage and expansion stage | Time to remission(TTR) is defined as the time from the date of ThisCART19A infusion until the date of first remission. | 12 months | 
| Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages | Track CAR T cells expansion in patients after infusion | 6 months | 
| Analysis the change characteristics of cytokines and immune effect cells number during dose escalation and expansion stages | Analysis the effect cells and cytokines in patient after infusion | 3 months | 
| Analysis the severity and Incidence of Adverse Events in each dose level during dose expansion stage | Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, or the adverse events with special attention | 3 months | 
| Analysis the immunogenicity(anti-therapeutic antibody and neutralizing antibody) of CAR-T cells after infusion |  | 12 months |