PD1-CD19-CART in Patients With r/r B-cell Lymphoma

NCT04213469 | Completed

• 1 other identifier: 2019-CAR-00CH1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (2)

• Objective response rate (ORR)

  Baseline up to 3 months after T cell infusion

• Progress free survival (PFS)

  Baseline up to 3 months after T cell infusion

Study Arms (1)

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.

Biological: PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells

Interventions

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

Also known as: PD1-CD19-CART

PD1-CD19-CART

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have the capacity to give informed consent;
• ALL patients with the age between 18 and 70 years old;
• Expected survival \>3 moths;
• With no severe heart and lung disease;
• Previously confirmed diagnosis as CD19+ NHL within 6 months;
• Hematological index as following, white blood cell (WBC)≥1.5×10\^9/L，absolute neutrophil count (ANC) ≥0.8×10\^9/L, Platelet count≥50×109/L, Hemoglobin (Hgb) ≥ 90mg/L, lymphocyte count≥ 0.4×10\^9/L；
• Blood biochemical index as no more than 1.5\* ULN, including total bilirubin (TBIL), transglutaminase (AST), alanine aminotransferase (AST), Creatinine (SCr), Urea in patients with no tumor metastasis in liver and kidney; Blood biochemical index no more than 5\* ULN in patients with tumor metastasis in liver and kidney;
• With a stable cardiac function, the left ventricular ejection fraction (LVEF) ≥ 55%;
• Virological tests were negative for EBV, CMV, HIV, TP and HCV; a negative HBV DNA test is acceptable if HBsAg is positive;
• ECOG \<2;
• Relapsed or refractory (r/r) NHL including, Diffuse large B cell lymphoma(DLBCL, NOS), stage Ⅲ-Ⅳ;Primary mediastinal large B-cell lymphoma (PMBL), stage Ⅲ-Ⅳ; High grade B-cell lymphoma (HGBL), stage Ⅲ-Ⅳ; Mantle cell lymphoma (MCL), stage Ⅲ-Ⅳ; follicular lymphoma (FL), stage Ⅲ-Ⅳ and with aggression. r/r NHL defined as following, demonstrate disease that persists or relapse after achieving complete response (CR) after \> 2 cycles of standard chemotherapy, or relapse after autologous hematopoietic stem cell transplantation (auto-HSCT), or not achieving CR after auto-HSCT.

You may not qualify if:

• Pregnant or lactating women;
• With a pregnancy plan in the next 2 years;
• Prior treatment of anti-GVHD therapy;
• Acceptance of allogeneic stem cell transplant (ASCT);
• Isolated extramedullary relapse of ALL;
• Severe mental disorders, active autoimmune diseases, active infectious diseases, severe cardiovascular diseases;
• Partial prothrombin time or activated partial thromboplastin time or international standardized ratio \> 1.5\*ULN without anticoagulant treatment;
• History of other type of maligant tumors;
• Any circumstances that possibly increase the risk of subjects or interfere with study results, which judged by investigator.

Sponsors & Collaborators

• Bioray Laboratories: lead
• First Affiliated Hospital of Zhejiang University: collaborator

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

Related Publications (4)

• 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.

  PMID: 37251628 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.

  PMID: 37192741 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.

  PMID: 36045296 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.

  PMID: 35468680 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• He Huang, Prof

  the First Affliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will receive one of the three doses of 2\*10\^6/kg, 4\*10\^6/kg,6\*10\^6/kg.

Study Record Dates

• First Submitted: December 26, 2019
• First Posted: December 30, 2019
• Study Start: March 13, 2020
• Primary Completion: November 1, 2021
• Study Completion: November 10, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)