Cord Blood-derived CAR-NK Cells Targeting CD19 for Refractory/Relapsed Central Nervous System Lymphoma

NCT06827782 | Enrolling By Invitation Phase 1

• 1 other identifier: ID2024482
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to evaluate the safety and efficacy of cord blood-derived CAR-NK019 in the treatment of refractory/relapsed central nervous system lymphoma.

Conditions

Refractory/Recurrent Central Nervous System Lymphoma

Keywords

Refractory or recurrent; central nervous system lymphoma; Diffuse large B cell lymphoma; CAR-NK

Outcome Measures

Primary Outcomes (1)

• Incidence of dose limiting toxicity (DLTs)

  To evaluate the safety, tolerability, and determine the recommended dosage of cord blood-derived Anti-CD19 CAR-NK Cell Therapy for refractory/relapsed central nervous system lymphoma

  Up to 28 days

Secondary Outcomes (5)

• Complete response rate (CR)

  3 months

• Overall response rate (ORR)

  3 months

• Progression free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Duration of response (DOR)

  Up to 2 years

Study Arms (1)

CB CAR-NK019

EXPERIMENTAL

Biological: anti-CD19 CAR-NK cells

Interventions

anti-CD19 CAR-NK cells BIOLOGICAL

lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19 CAR

CB CAR-NK019

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with refractory/recurrent CNS lymphoma must meet all of the following criteria to be eligible:
• Voluntarily participate in the study and sign the informed consent;
• Age 18-75 years old, male or female;
• Diffuse large B-cell lymphoma (DLBCL) was confirmed by histology. CD19 expression was positive by lymphoma pathology or flow cytometry, and CD19 expression was ≥20% by IHC.
• Imaging showed no evidence of systemic lymphoma;
• Meets any of the following definitions for refractory/relapsed CNS lymphoma: no complete response has been achieved with prior 2-line regimen including methotrexate or cytarabine-based regimen; Disease progression during any treatment; The stable time of disease after effective treatment is less than 6 months; Disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation.
• Imaging showed the presence of at least one measurable lesion, with a minimum diameter of ≥10mm;
• Expected survival ≥3 months;
• ECOG score 0-3 points;
• Adequate organ function reserve:
• alanine aminotransferase, ASpartate aminotransferase ≤ 2.5× UNL (upper limit of normal);
• Creatinine clearance (Cockcroft-Gault method) ≥60 mL/min;
• Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
• Glomerular filtration rate \>50ml/min
• cardiac ejection fraction (EF) ≥45%;

You may not qualify if:

• Subjects who meet any of the following criteria will not be admitted to the study:
• Allergic to any of the components of cell products;
• History of other tumors;
• Acute grade II-IV (Glucksberg standard) GvHD or generalized chronic GvHD occurred after previous allogeneic hematopoietic stem cell transplantation; Or are receiving anti-GVHD treatment;
• Have received gene therapy within the past 3 months;
• Active infections requiring treatment (except simple urinary tract infections, bacterial pharyngitis), but prophylactic antibiotic, antiviral and antifungal infection treatment is permitted;
• Persons infected with hepatitis B (HBsAg positive, but HBV-DNA\<103 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV-infected persons;
• Subjects with Grade III or IV cardiac dysfunction according to the New York Heart Association's cardiac function grading criteria;
• Patients who received antitumor therapy in the early stage but did not recover toxicity (CTCAE 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia);
• Previous history of epilepsy, autoimmune encephalitis, cerebral infarction or cerebral hemorrhage within 6 months;
• Whole-body enhanced CT or PET/CT suggests evidence of systemic lymphoma;
• Lactating women who are unwilling to stop breastfeeding;
• Any other circumstances that the investigator believes may increase the risk to the subject or interfere with the test results;
• Patients requiring more than 10mg of dexamethasone per day for 3 days prior to enrollment;
• Patients who cannot tolerate ommaya capsule implantation;

Sponsors & Collaborators

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

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2024
• First Posted: February 14, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 15, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)