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| Name | Class |
|---|---|
| First Affiliated Hospital of Zhejiang University | OTHER |
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This is an open label, single-site, dose-escalation study in up to 25 participants with relapse/refractory B-NHL. This study aims to evaluate the safety and efficacy of the treatment with PD1-CD19-CART.
PD1-CD19-CART is a kind of chimeric antigen T cell targeting CD19 with both CD19-CAR gene integration and also PD1 knockout by one-step gene-editing. After completion of study treatment, subject participation for this study will be followed up to 15 years post T cell infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PD1-CD19-CART | Experimental | Patients undergo leukapheresis. Patients will receive a lymphodepletion chemotherapy with cyclophosphamide and fludarabine before CART infusion. A dose of PD1-CD19-CART will be infused on day 0. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells | Biological | Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| MTD | MTD will be determined based on DLTs observed during the first 28 days of study treatment. | up to 28 days after T cell infusion |
| RP2D | RP2D will be determined based on MTD and efficiency during the first 28 days of study treatment. | up to 28 days after T cell infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed. | Baseline up to 3 months after T cell infusion |
| Progress free survival (PFS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| He Huang, Prof | the First Affliated Hospital, Zhejiang University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital, Zhejiang University School of Medicine | Hangzhou | Zhejiang | 310003 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37251628 | Derived | Hu Y, Zu C, Zhang M, Wei G, Li W, Fu S, Hong R, Zhou L, Wu W, Cui J, Wang D, Du B, Liu M, Zhang J, Huang H. Safety and efficacy of CRISPR-based non-viral PD1 locus specifically integrated anti-CD19 CAR-T cells in patients with relapsed or refractory Non-Hodgkin's lymphoma: a first-in-human phase I study. EClinicalMedicine. 2023 May 18;60:102010. doi: 10.1016/j.eclinm.2023.102010. eCollection 2023 Jun. | |
| 37192741 |
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| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Patients will receive one of the three doses of 2*10^6/kg, 4*10^6/kg,6*10^6/kg.
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|
Assessed using modified Lugano classification response criteria for lymphoma (2014) |
| Baseline up to 3 months after T cell infusion |
| Derived |
| Zhou L, Fu W, Wu S, Xu K, Qiu L, Xu Y, Yan X, Zhang Q, Zhang M, Wang L, Hong R, Chang AH, Yu J, Fu S, Kong D, Li L, Wang Y, Li Z, Jiang H, Huang J, Liu Z, Su N, Wei G, Hu Y, Huang H. Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study. Br J Haematol. 2023 Aug;202(3):517-524. doi: 10.1111/bjh.18873. Epub 2023 May 16. |
| 36045296 | Derived | Zhang J, Hu Y, Yang J, Li W, Zhang M, Wang Q, Zhang L, Wei G, Tian Y, Zhao K, Chen A, Tan B, Cui J, Li D, Li Y, Qi Y, Wang D, Wu Y, Li D, Du B, Liu M, Huang H. Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL. Nature. 2022 Sep;609(7926):369-374. doi: 10.1038/s41586-022-05140-y. Epub 2022 Aug 31. |
| 35468680 | Derived | Golubovskaya V. CAR-T Cells Targeting Immune Checkpoint Pathway Players. Front Biosci (Landmark Ed). 2022 Apr 2;27(4):121. doi: 10.31083/j.fbl2704121. |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |