- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04213469
PD1-CD19-CART in Patients With r/r B-cell Lymphoma
January 4, 2024 updated by: Bioray Laboratories
a Safety and Efficacy Evaluation of PD1-CD19-CART in Patients With Relapse/Refractory B-cell Lymphoma
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
20
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Zhejiang
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Hangzhou, Zhejiang, China, 310003
- The First Affiliated Hospital, Zhejiang University School of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PD1-CD19-CART
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.
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Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD
Time Frame: up to 28 days after T cell infusion
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MTD will be determined based on DLTs observed during the first 28 days of study treatment.
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up to 28 days after T cell infusion
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RP2D
Time Frame: up to 28 days after T cell infusion
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RP2D will be determined based on MTD and efficiency during the first 28 days of study treatment.
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up to 28 days after T cell infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: Baseline up to 3 months after T cell infusion
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Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed.
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Baseline up to 3 months after T cell infusion
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Progress free survival (PFS)
Time Frame: Baseline up to 3 months after T cell infusion
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Assessed using modified Lugano classification response criteria for lymphoma (2014)
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Baseline up to 3 months after T cell infusion
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: He Huang, Prof, the First Affliated Hospital, Zhejiang University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 13, 2020
Primary Completion (Actual)
November 1, 2021
Study Completion (Actual)
November 10, 2023
Study Registration Dates
First Submitted
December 26, 2019
First Submitted That Met QC Criteria
December 26, 2019
First Posted (Actual)
December 30, 2019
Study Record Updates
Last Update Posted (Actual)
January 5, 2024
Last Update Submitted That Met QC Criteria
January 4, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2019-CAR-00CH1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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