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

Primary Purpose

B-cell Lymphoma

Status
Active
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
Sponsored by
Bioray Laboratories
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The First Affiliated Hospital, Zhejiang University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PD1-CD19-CART

Arm Description

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.

Outcomes

Primary Outcome Measures

MTD
MTD will be determined based on DLTs observed during the first 28 days of study treatment.
RP2D
RP2D will be determined based on MTD and efficiency during the first 28 days of study treatment.

Secondary Outcome Measures

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.
Progress free survival (PFS)
Assessed using modified Lugano classification response criteria for lymphoma (2014)

Full Information

First Posted
December 26, 2019
Last Updated
September 28, 2022
Sponsor
Bioray Laboratories
Collaborators
First Affiliated Hospital of Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT04213469
Brief Title
PD1-CD19-CART in Patients With r/r B-cell Lymphoma
Official Title
a Safety and Efficacy Evaluation of PD1-CD19-CART in Patients With Relapse/Refractory B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 13, 2020 (Actual)
Primary Completion Date
November 1, 2021 (Actual)
Study Completion Date
April 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioray Laboratories
Collaborators
First Affiliated Hospital of Zhejiang University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
Patients will receive one of the three doses of 2*10^6/kg, 4*10^6/kg,6*10^6/kg.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PD1-CD19-CART
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
PD1 specific integrated anti-CD19 Chimeric Antigen Receptor T Cells
Other Intervention Name(s)
PD1-CD19-CART
Intervention Description
Gene editing autologous T cells with anti-CD19 ScFv expression and knockout of PD1
Primary Outcome Measure Information:
Title
MTD
Description
MTD will be determined based on DLTs observed during the first 28 days of study treatment.
Time Frame
up to 28 days after T cell infusion
Title
RP2D
Description
RP2D will be determined based on MTD and efficiency during the first 28 days of study treatment.
Time Frame
up to 28 days after T cell infusion
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Proportion of patients in whom a response among complete response and partial response as defined by standard disease-specific criteria, will be observed.
Time Frame
Baseline up to 3 months after T cell infusion
Title
Progress free survival (PFS)
Description
Assessed using modified Lugano classification response criteria for lymphoma (2014)
Time Frame
Baseline up to 3 months after T cell infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
He Huang, Prof
Organizational Affiliation
the First Affliated Hospital, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital, Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36045296
Citation
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.
Results Reference
derived
PubMed Identifier
35468680
Citation
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.
Results Reference
derived

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

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