Clinical Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

NCT ID: NCT05667155

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-15
• Study Completion Date: 2025-12-30

Brief Summary

To study the safety and efficacy of cord blood-derived CAR-NK cells targeting CD19/CD70 in patients with B-cell non-Hodgkin's lymphoma

Detailed Description

This is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualCAR-NK19/70 cells in patients with B-cell non-Hodgkin lymphoma.9-18 patients are planned to be enrolled in the dose-escalation trial (2×10^6 cells/kg, 4×10^6 cells/kg, 8×10^6 cells/kg) . Each dose was given once a week for 3 weeks.The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled to estimate the safety and efficacy of CB CAR-NK019 under the best dose.

Conditions

B-cell Non Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CB dualCAR-NK19/70

All subjects were intravenously administrated with CB dualCAR-NK19/70

Group Type: EXPERIMENTAL

CB dualCAR-NK19/70

Intervention Type: BIOLOGICAL

Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15

Interventions

CB dualCAR-NK19/70

Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenbin Wenbin

Role: PRINCIPAL_INVESTIGATOR

2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Locations

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hanzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenbin Qian, PhD

Role: CONTACT

qianwb@zju.edu.cn

+8613605801032

Hui Liu, PhD

Role: CONTACT

sylen@zju.edu.cn

13819198629

Facility Contacts

Wenbin Qian, PhD

Role: primary

qianwb@zju.edu.cn

+8613605801032

Hui Liu, PhD

Role: backup

sylen@zju.edu.cn

13819198629

Other Identifiers

2022-088

Identifier Type: -

Identifier Source: org_study_id