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

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • The First Affiliated Hospital, Zhejiang University School of Medicine

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:

  1. Have the capacity to give informed consent;
  2. ALL patients with the age between 18 and 70 years old;
  3. Expected survival >3 moths;
  4. With no severe heart and lung disease;
  5. Previously confirmed diagnosis as CD19+ NHL within 6 months;
  6. 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；
  7. 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;
  8. With a stable cardiac function, the left ventricular ejection fraction (LVEF) ≥ 55%;
  9. Virological tests were negative for EBV, CMV, HIV, TP and HCV; a negative HBV DNA test is acceptable if HBsAg is positive;
  10. ECOG <2;
  11. 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:

  1. Pregnant or lactating women;
  2. With a pregnancy plan in the next 2 years;
  3. Prior treatment of anti-GVHD therapy;
  4. Acceptance of allogeneic stem cell transplant (ASCT);
  5. Isolated extramedullary relapse of ALL;
  6. Severe mental disorders, active autoimmune diseases, active infectious diseases, severe cardiovascular diseases;
  7. Partial prothrombin time or activated partial thromboplastin time or international standardized ratio > 1.5*ULN without anticoagulant treatment;
  8. History of other type of maligant tumors;
  9. 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.
Biological: PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1
Other Names:
  • PD1-CD19-CART

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
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
Time Frame: up to 28 days after T cell infusion
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: Baseline up to 3 months after T cell infusion
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)
Time Frame: Baseline up to 3 months after T cell infusion
Assessed using modified Lugano classification response criteria for lymphoma (2014)
Baseline up to 3 months after T cell infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bioray Laboratories

Collaborators

First Affiliated Hospital of Zhejiang University

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

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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