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Clinical Study of HLA Haploidentical CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL

Primary Purpose

B-cell Non Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-CD19 CAR-NK
Sponsored by
Second Affiliated Hospital, School of Medicine, Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Non Hodgkin Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Volunteer to participate in this study and sign an informed consent form;
  2. Age 18-75 years old, no gender limit;
  3. Histologically diagnosed as diffuse large B-cell lymphoma (DLBCL), transforming follicular lymphoma (TFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL) and other inert B-cells NHL conversion type:

    • Refractory or relapsed DLBCL refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ;
    • Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors;
    • Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment;
    • Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines;
  4. At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;
  5. The expected survival period is ≥12 weeks;
  6. The puncture section of the tumor tissue was positive for CD19 expression;
  7. ECOG score 0-2 points;
  8. Sufficient organ function reserve:

    • Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
    • Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
    • Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
    • Glomerular filtration rate>50Ml/min
    • Cardiac ejection fraction (EF) ≥50%;
    • Under natural indoor air environment, basic oxygen saturation>92%
  9. Allow a previous stem cell transplantation
  10. The approved anti-B-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication;
  11. Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;
  12. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial
  13. Two tests for the new coronavirus were negative.

Exclusion Criteria:

  1. Those who have a history of allergies to any of the ingredients in cell products;
  2. History of other tumors
  3. Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment;
  4. Have received gene therapy in the past 3 months;
  5. Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed;
  6. Hepatitis B (HBsAg positive, but HBV-DNA <103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including But not limited to people living with HIV;
  7. According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV.

    Impaired subjects;

  8. Those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the CTCAE 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss);
  9. Subjects with a history of epilepsy or other central nervous system diseases;
  10. Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma;
  11. Have received any other drugs that target CD19;
  12. Women who are breastfeeding and unwilling to stop breastfeeding;
  13. Any other situation that the investigator believes may increase the risk of the subject or interfere with the results of the test.

Sites / Locations

  • 2nd Affiliated Hospital, School of Medicine, Zhejiang UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-NK019

Arm Description

All subjects were intravenously administrated with CAR-NK019

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicity (DLTs)
To evaluate the safety, tolerability, and determine the recommended dosage of Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma
The overall response rate(ORR)
To determine the anti-tumor effectivity of CAR-NK019

Secondary Outcome Measures

Overall survival (OS)
To determine the anti-tumor effectivity of CAR-NK019
progression free survival (PFS)
To determine the anti-tumor effectivity of CAR-NK019
Pharmacokinetics of CAR positive cells
The copy number of CAR DNA was measured at the preset follow-up time point.
Pharmacokinetics of CAR-NK cells
The duration of CAR-positive NK cells in circulation was measured by FACs

Full Information

First Posted
May 7, 2021
Last Updated
May 13, 2021
Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University
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1. Study Identification

Unique Protocol Identification Number
NCT04887012
Brief Title
Clinical Study of HLA Haploidentical CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL
Official Title
Clinical Study of HLA Haploidentical CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2021 (Actual)
Primary Completion Date
May 1, 2022 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University

4. Oversight

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

5. Study Description

Brief Summary
To study the safety and effectiveness of HLA haploidentical CAR-NK cells targeting CD19 in patients with B-cell non-Hodgkin's lymphoma

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CAR-NK019
Arm Type
Experimental
Arm Description
All subjects were intravenously administrated with CAR-NK019
Intervention Type
Biological
Intervention Name(s)
anti-CD19 CAR-NK
Other Intervention Name(s)
CAR-NK019
Intervention Description
lentiviral vector-transducted HLA haploidentical NK cells to express anti-CD19 CAR
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicity (DLTs)
Description
To evaluate the safety, tolerability, and determine the recommended dosage of Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma
Time Frame
Up to 28 days
Title
The overall response rate(ORR)
Description
To determine the anti-tumor effectivity of CAR-NK019
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
To determine the anti-tumor effectivity of CAR-NK019
Time Frame
Up to 2 years
Title
progression free survival (PFS)
Description
To determine the anti-tumor effectivity of CAR-NK019
Time Frame
Up to 2 years
Title
Pharmacokinetics of CAR positive cells
Description
The copy number of CAR DNA was measured at the preset follow-up time point.
Time Frame
Up to 2 years
Title
Pharmacokinetics of CAR-NK cells
Description
The duration of CAR-positive NK cells in circulation was measured by FACs
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Volunteer to participate in this study and sign an informed consent form; Age 18-75 years old, no gender limit; Histologically diagnosed as diffuse large B-cell lymphoma (DLBCL), transforming follicular lymphoma (TFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL) and other inert B-cells NHL conversion type: Refractory or relapsed DLBCL refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ; Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors; Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment; Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines; At least one measurable lesion with the longest diameter ≥ 1.5 cm exists; The expected survival period is ≥12 weeks; The puncture section of the tumor tissue was positive for CD19 expression; ECOG score 0-2 points; Sufficient organ function reserve: Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value); Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min; Serum total bilirubin and alkaline phosphatase ≤1.5× UNL; Glomerular filtration rate>50Ml/min Cardiac ejection fraction (EF) ≥50%; Under natural indoor air environment, basic oxygen saturation>92% Allow a previous stem cell transplantation The approved anti-B-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication; Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation; Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial Two tests for the new coronavirus were negative. Exclusion Criteria: Those who have a history of allergies to any of the ingredients in cell products; History of other tumors Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment; Have received gene therapy in the past 3 months; Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed; Hepatitis B (HBsAg positive, but HBV-DNA <103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including But not limited to people living with HIV; According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV. Impaired subjects; Those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the CTCAE 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss); Subjects with a history of epilepsy or other central nervous system diseases; Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma; Have received any other drugs that target CD19; Women who are breastfeeding and unwilling to stop breastfeeding; Any other situation that the investigator believes may increase the risk of the subject or interfere with the results of the test.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenbin Qian
Phone
+8613605801032
Email
qianwb@zju.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenbin Qian
Organizational Affiliation
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
2nd Affiliated Hospital, School of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenbing Qian
Phone
+8613605801032
Email
qianwb@zju.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Clinical Study of HLA Haploidentical CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL

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