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/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

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

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: NCT05667155 on ClinicalTrials.gov

What this trial studies

This clinical study investigates the safety and efficacy of cord blood-derived CAR-NK cells that target CD19 and CD70 in patients with refractory or relapsed B-cell non-Hodgkin lymphoma. It is a single-center, open-label, one-arm, dose-escalation trial where patients will receive escalating doses of CAR-NK cells over three weeks. The primary endpoints include dose-limiting toxicity and maximum tolerated dose, while secondary endpoints focus on overall response rates, overall survival, and progression-free survival. The study aims to determine the optimal dose for further evaluation in a larger cohort.

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 chemotherapy.

Not a fit: Patients with non-B-cell lymphomas or those who have not previously received chemotherapy may not benefit from this study.

Why it matters

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

How similar studies have performed: While the use of CAR-NK cells is a relatively novel approach, similar studies targeting B-cell malignancies have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in the study and sign the informed consent;
2. Age 18-75, male and female;
3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other inert B-cell NHL transforming types:

(1)refractory or recurrent DLBCL and tFL must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large B cell lymphoma (research SCHOLAR - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; The stable time of the disease is equal to or less than 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include CD20 single resistance (unless the subjects for CD20 negative) and anthracycline-based;

4. There was at least one measurable lesion with the longest diameter ≥1.5 cm;

5. Predicted survival ≥12 weeks;

6. The expression of CD19 or CD70 in biopsy sections of tumor tissue was positive;

7. ECOG score 0-2;

8. Adequate reserve of organ functions:

1. cereal third transaminase, aspartate aminotransferase 2.5 x or less UNL (upper limit of normal);
2. creatinine clearance (Cockcroft - Gault method) or 60 mL/min.
3. serum total bilirubin and alkaline phosphatase (1.5 x or less UNL.
4. glomerular filtration rate \> 50 mL/min
5. heart ejection fraction (EF) 45% or higher;
6. indoor natural air environment, basic oxygen saturation \> 92%
7. blood routine: neutrophils absolute number \> 1000 cells/mm3, platelet count 45 x109, 8.0 g/dL hemoglobin;

9. Allowed to have received a previous stem cell transplant

10. Approved anti-B-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. The eluting period of targeted drug regimens without chemotherapy was 2 weeks;

11. Patients who had previously received CAR T cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted;

12. Female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial

13. Two tests have come back negative for COVID-19.

Exclusion Criteria:

1. Allergic to any of the components of cell products;
2. History of other tumors;
3. Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; Or being treated with anti-GVHD;
4. Had received gene therapy in the past 3 months;
5. Active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed;
6. Subjects 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;
7. Subjects with Grade III or IV cardiac insufficiency according to the New York Heart Association Cardiac Function Grading criteria;
8. Patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (CTCAE 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia);
9. Subjects with a history of epilepsy or other central nervous system diseases;
10. Skull enhanced CT or MRI showing evidence of central nervous system lymphoma;
11. Lactating women who refuse to stop breastfeeding;
12. Any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.

Where this trial is running

Hanzhou, Zhejiang

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

Study contacts

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

Conditions B-cell Non Hodgkin Lymphoma