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

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

Study Overview

• Status: Recruiting
• Conditions: B-cell Non Hodgkin Lymphoma
• Intervention / Treatment: Biological: anti-CD19 CAR-NK

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Wenbing Qian; Phone Number: +8613605801032; Email: qianwb@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 28 days
The overall response rate(ORR)	To determine the anti-tumor effectivity of CAR-NK019	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	To determine the anti-tumor effectivity of CAR-NK019	Up to 2 years
progression free survival (PFS)	To determine the anti-tumor effectivity of CAR-NK019	Up to 2 years
Pharmacokinetics of CAR positive cells	The copy number of CAR DNA was measured at the preset follow-up time point.	Up to 2 years
Pharmacokinetics of CAR-NK cells	The duration of CAR-positive NK cells in circulation was measured by FACs	Up to 2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 14, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: IR2021002168

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