Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cell Malignancies 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 a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy in china.

Detailed Description
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This is a phase 1, single-center, nonrandomized, open-label, dose-escalation and dose expansion study to evaluate the safety and efficacy of ThisCART19A in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.

Official Title
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A Single Dose-escalation Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Targeting CD19 (ThisCART19A) in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy

Conditions
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Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited

Intervention / Treatment
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* Drug: ThisCART19A
* Drug: Fludarabine Pill
* Drug: Cyclophosphamide
* Drug: VP-16 Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with relapsed or refractory acute lymphocytic leukemia, or lymphoma； No gender limitation, Age 14 years to 75 years (both upper and lower limits included)； Failing to autologous CAR-T therapy； Should be confirmed Cluster of differentiation(CD)19 positive； The expected survival time is ≥12 weeks; ECOG score 0-1; Measurable or detectble disease at time of enrollment. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function； 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 (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment; Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment； The presence of central nervous system involvement； 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)； Receive allogeneic hematopoietic stem cell transplantation less than 100 days； Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included)； Patients who are receiving 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ThisCART19A cells infusion<br>In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia. | Drug: ThisCART19A<br>* ThisCART19A is a new type CAR-T therapy for patients with r/r B Cell Malignancy .<br>Drug: Fludarabine Pill<br>* Fludarabine is used for lymphodepletion.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide is used for lymphodepletion.<br>Drug: VP-16 Protocol<br>* VP-16 is used for lymphodepletion.<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 B Cell Malignancy in each dose level 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 within 3 months during dose expansion stage | For Acute Lymphoblastic Leukemia (ALL), Objective response rate(ORR) is the percentage of patients who achieve Complete Response (CR) or Complete Response With Incomplete Hematologic Recovery (CRi); for lymphoma, ORR is the incidence of either a complete response (CR) or a partial response (PR). | 3 months | 
| Minimum Residual Disease (MRD) Negative Remission Rate within 3 months during dose expansion stage | MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response(DOR) during dose escalation stage and expansion stage | DOR was defined as the time from first CR/CRi or PR to relapse or any death in the absence of documented relapse. | 24 months | 
| Relapse-free Survival (RFS) | RFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse or death from any cause. | 24 months | 
| Event-free Survival (EFS) | EFS is defined as the time from the date of ThisCART19A infusion to the date of disease relapse, progression, genetic relapse or death from any cause. | 24 months | 
| Overall Survival (OS) | OS is defined as the time from the date of ThisCART19A infusion to the date of death from any cause. | 24 months |