Clinical Study of CAR-iNKT Cells in the Treatment of Relapsed/Refractory/High-risk B-cell Tumors

Study Overview
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Brief Summary
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This study aims to evaluate the safety and feasibility of hCD19.IL15.CAR-iNKT cells in treating patients with relapsed/refractory/high-risk B-cell tumors.

Detailed Description
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CD19 CAR-T has been shown to treat a variety of refractory or recurrent B-cell tumors. Because most CAR-T cells are generated from the patient's own T cells and are individualized products, and there are individual differences between patients, the generation of customized CAR-T cells is an expensive and time-consuming process. Universal CAR- iNKT cells are an ideal product for cell therapy. In this study, we prepared universal iNKT cells expressing hCD19 CAR and IL-15 to treat refractory, relapsed, or high-risk B-cell tumors.

Official Title
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Clinical Study of CAR-iNKT Cells in the Treatment of Relapsed/Refractory/High-risk B-cell Tumors

Conditions
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Acute Lymphoblastic Leukemia, B-cell Lymphoma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: hCD19.IL15.CAR-iNKT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 5-70 years; The patient's ECOG score was ≤2, and the expected survival time of > was 12 weeks. The patient was diagnosed with B-cell tumor by pathological and histological examination and had no effective treatment options, such as recurrence after chemotherapy or hematopoietic stem cell transplantation. Or the patient voluntarily chooses the infusion of CAR-INKT cells as the first treatment. B cell tumors include the following three types: B-cell acute lymphocytic leukemia (B-ALL); Inert B-cell lymphoma (CLL, FL, MZL, LPL, HCL); Aggressive B-cell lymphoma (DLBCL, BL, MCL); Subject: Residual lesions remain after primary treatment and are not suitable for HSCT (Auto/Allo-HSCT); relapse after complete response (CR1) and unsuitable for allogeneic/autologous HSCT; Patients with high risk factors; relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy. having measurable or evaluable lesions; The main tissues and organs of the patient function well: Liver function: ALT/AST < 3 times the upper limit of normal (ULN); Renal function: creatinine < 220μmol/L; Lung function: indoor oxygen saturation ≥95%; Heart function: left ventricular ejection fraction (LVEF) ≥40%. Patients or their legal guardians voluntarily participate and sign the informed consent. Exclusion Criteria: Pregnant or lactating women, or women who plan to become pregnant within six months; Infectious diseases (e.g. HIV, active hepatitis B or C infection, active tuberculosis, etc.); GVHD; Abnormal vital signs and failure to cooperate with the examination; People with mental or mental illness who are unable to cooperate with treatment and efficacy evaluation; People with high allergic constitution or severe allergic history, especially those allergic to IL-2; Subjects with systemic infection or severe local infection need anti-infection therapy; Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs; Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification ≥III); Doctors believe that there are other reasons for not being included in treatment.

Ages Eligible for Study
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Minimum Age: 5 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: hCD19.IL15.CAR-iNKT cells<br>Dose escalation follows the accelerated titration and the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects. | Drug: hCD19.IL15.CAR-iNKT<br>* Universal hCD19.IL15.CAR-iNKT cells by a single infusion intravenously will be given in escalating doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Baseline up to 28 days after T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRD negative overall response rate (MRD- ORR) | Assessment of MRD negative overall response rate (MRD- ORR) at 3 months of treatment | 3 months | 
| Overall response rate (ORR) | Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24 | Month 6, 12, 18 and 24 | 
| Event-free survival (EFS) | Assessment of EFS at Month 6, 12, 18 and 24 | Month 6, 12, 18 and 24 | 
| Overall survival (OS) | Assessment of OS at Month 6, 12, 18 and 24 | Month 6, 12, 18 and 24 |