Treatment of Children CD19+ Leukemia and Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell Therapy

Study Overview
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Brief Summary
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This is a single arm, open-label, early phase Ⅰ study, to determine the safety and efficacy of CD19-TriCAR-T and CD19-TriCAR-SILK cell therapy in Children CD19+ Leukemia Non-Hodgkin lymphoma treatment.

Detailed Description
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CD19-TriCAR contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the CD19-TriCAR-T/SILK to simultaneously targeting the CD19 positive Leukemia or Non-Hodgkin lymphoma，blocking the inhibitory PD-L1 signal and stimulating innate T/NK cell activation and expansion, thus make it a tri- functional CAR (Tri-CAR). CD19-TriCAR-T is an autologous tri-functional CAR-T cell therapy, CD19-TriCAR-SILK is an Allogeneic tri-functional CAR- NK cell therapy, patients ineligible for leukapheresis or CAR-T therapy will be recommended for CD19-TriCAR-SILK therapy.

Official Title
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Adoptive Immunotherapy for Children CD19+ Leukemia and Non-Hodgkin Lymphoma With CD19-TriCAR-T/SILK Cell

Conditions
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Non-Hodgkin Lymphoma of Intestine, Leukemia

Intervention / Treatment
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* Biological: CD19-TriCAR-T/SILK


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For children CD19 positive B cell leukemia： All subjects must personally sign and date the Informed Consent before initiating any study specific procedures or activities; All subjects must be able to comply with all the scheduled procedures in the study; CD19-positive B-cell leukemia with histology or cytology confirmed recurrence after treatment; or progression during treatment; or after first line treatment getting a MRD negative, 2 times of MRD show>0.01% but without bone marrow morphology recurrence; At least one measurable lesion; Aged <18 years; or diagnosised at the age of less than 18 and relapsed within three years， determined by the investigator; Expected survival ≥12 weeks; Eastern cooperative oncology group(ECOG) performance status of≤2; Before CD19-TriCAR-T/SILK cell infusion, systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; All other treatment induced adverse events must have been resolved to ≤grade 1; For children CD19 positive B cell lymphoma： All subjects must personally sign and date the Informed Consent before initiating any study specific procedures or activities; All subjects must be able to comply with all the scheduled procedures in the study; CD19-positive B-cell lymphoma with histology or cytology confirmed recurrence after treatment，defined as one or more of the following: disease progression during standard therapy；recurrence after termination of treatment；relapse after autologous hematopoietic stem cell transplantation；not suitable for stem cell transplantation or abandon stem cell transplantation due to conditional restrictions; At least one measurable lesion; Aged <18 years; or diagnosised at the age of less than 18 and relapsed within three years， determined by the investigator; Expected survival ≥12 weeks; Eastern cooperative oncology group(ECOG) performance status of≤2; Before CD19-TriCAR-T/SILK cell infusion, systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks; All other treatment induced adverse events must have been resolved to ≤grade 1; Exclusion Criteria: Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. (Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment); Patients with symptomatic central nervous system metastasis, intracranial metastasis, and cancer cells found in cerebrospinal fluid are not recommended to participate in this study. Symptom free or post-treatment stable disease or disappearance of lesions should not be excluded. The specific selection is ultimately determined by the investigator; Lactating women or women of childbearing age who plan to conceive during the time period; Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive); Known history of infection with HIV; Subjects need systematic usage of corticosteroid; Subjects need systematic usage of immunosuppressive drug; Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study; Other reasons the investigator consider the patient may not be suitable for the study.

Ages Eligible for Study
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Maximum Age: 18 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-TriCAR-T/NK（SILK）<br>CD19-TriCAR-T/SILK cells will be administered intravenously | Biological: CD19-TriCAR-T/SILK<br>* A conditioning chemotherapy regimen of fludarabine and cyclophosphamide may be administered, followed by a single infusion of CD19-TriCAR-T cells or 4 repeat infusions of CD19-TriCAR-SILK cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safty (Incidence of treatment-related adverse events as assessed by CTCAE v4.03) | Incidence of treatment-related adverse events as assessed by CTCAE v4.03 | 24 monthes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma) | Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma | 24 monthes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin Lymphoma, Leukemia, children, CD19, CAR-T, TriCAR-T, TriCAR-SILK