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

Sponsor
Second Affiliated Hospital, School of Medicine, Zhejiang University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04887012
Collaborator
(none)
25
Enrollment
1
Location
1
Arm
36
Anticipated Duration (Months)
0.7
Patients Per Site Per Month

Study Details

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

Condition or Disease Intervention/Treatment Phase
  • Biological: anti-CD19 CAR-NK
 Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
25 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Clinical Study of HLA Haploidentical CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL
Actual Study Start Date :
May 1, 2021
Anticipated Primary Completion Date :
May 1, 2022
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: CAR-NK019

All subjects were intravenously administrated with CAR-NK019

Biological: anti-CD19 CAR-NK
lentiviral vector-transducted HLA haploidentical NK cells to express anti-CD19 CAR
Other Names:
  • CAR-NK019

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of dose limiting toxicity (DLTs) [Up to 28 days]

      To evaluate the safety, tolerability, and determine the recommended dosage of Anti-CD19 CAR-NK Cell Therapy for B-cell Non-Hodgkin Lymphoma

    2. The overall response rate(ORR) [Up to 2 years]

      To determine the anti-tumor effectivity of CAR-NK019

    Secondary Outcome Measures

    1. Overall survival (OS) [Up to 2 years]

      To determine the anti-tumor effectivity of CAR-NK019

    2. progression free survival (PFS) [Up to 2 years]

      To determine the anti-tumor effectivity of CAR-NK019

    3. Pharmacokinetics of CAR positive cells [Up to 2 years]

      The copy number of CAR DNA was measured at the preset follow-up time point.

    4. Pharmacokinetics of CAR-NK cells [Up to 2 years]

      The duration of CAR-positive NK cells in circulation was measured by FACs

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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;

    1. At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;

    2. The expected survival period is ≥12 weeks;

    3. The puncture section of the tumor tissue was positive for CD19 expression;

    4. ECOG score 0-2 points;

    5. 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%

    1. Allow a previous stem cell transplantation

    2. 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;

    3. Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;

    4. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial

    5. 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;

    1. 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);

    2. Subjects with a history of epilepsy or other central nervous system diseases;

    3. Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma;

    4. Have received any other drugs that target CD19;

    5. Women who are breastfeeding and unwilling to stop breastfeeding;

    6. Any other situation that the investigator believes may increase the risk of the subject or interfere with the results of the test.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 2nd Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou Zhejiang China 310009

    Sponsors and Collaborators

    • Second Affiliated Hospital, School of Medicine, Zhejiang University

    Investigators

    • Principal Investigator: Wenbin Qian, 2nd Affiliated Hospital, School of Medicine, Zhejiang University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Second Affiliated Hospital, School of Medicine, Zhejiang University
    ClinicalTrials.gov Identifier:
    NCT04887012
    Other Study ID Numbers:
    • IR2021002168
    First Posted:
    May 14, 2021
    Last Update Posted:
    May 14, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma, B-Cell

    Study Results

    No Results Posted as of May 14, 2021