Using cord blood-derived CAR-NK cells to treat B-cell non-Hodgkin lymphoma

Clinical Study of Cord Blood-derived CAR-NK Cells Targeting CD19 in the Treatment of Refractory/Relapsed B-cell NHL

This study is testing a new treatment using special immune cells from cord blood to see if it can help people with tough-to-treat B-cell non-Hodgkin lymphoma feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Hanzhou, Zhejiang)
• Trial ID: NCT05472558 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effectiveness of cord blood-derived CAR-NK cells that target CD19 in patients with refractory or relapsed B-cell non-Hodgkin lymphoma. It is an open-label, single-arm, dose-escalation study that plans to enroll 9-18 patients initially to determine the maximum tolerated dose (MTD) and assess dose-limiting toxicities (DLT). Following this, an additional 30 patients will be enrolled to further evaluate the safety and efficacy of the recommended dose. The primary endpoints include DLT and MTD, while secondary endpoints focus on overall response rates, overall survival, and progression-free survival.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with refractory or relapsed B-cell non-Hodgkin lymphoma who have previously undergone specific treatments.

Not a fit: Patients with early-stage B-cell non-Hodgkin lymphoma or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell non-Hodgkin lymphoma.

How similar studies have performed: While this approach is innovative, similar studies using CAR-NK cells have shown promise in other hematological malignancies.

Eligibility criteria

Inclusion 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.

Where this trial is running

Hanzhou, Zhejiang

• 2nd Affiliated Hospital, School of Medicine, Zhejiang University — Hanzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Wenbin Qian — 2nd Affiliated Hospital, School of Medicine, Zhejiang University
• Study coordinator: Wenbin Qian

Conditions B-cell Non Hodgkin Lymphoma