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

B-cell Non Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667155
• Other study ID #: 2022-088
• Status: Recruiting
• Phase: Phase 1
• Start date: December 15, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: February 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Wenbin Qian, PhD
• Phone: +8613605801032
• Email: qianwb[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 30, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Non Hodgkin Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• CB dualCAR-NK19/70
Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19/CD70 CAR and IL15

Locations

Country	Name	City	State
China	2nd Affiliated Hospital, School of Medicine, Zhejiang University	Hanzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 B-cell Non-Hodgkin Lymphoma	Up to 28 days
Secondary	Overall survival (OS)	To determine the anti-tumor effectivity of CB dualCAR-NK19/70	Up to 2 years
Secondary	Overall response rate (ORR)	To determine the anti-tumor effectivity of CB dualCAR-NK19/70	Up to 2 years
Secondary	Duration of response (DOR)	To determine the anti-tumor effectivity of CB dualCAR-NK19/70	Up to 2 years
Secondary	Complete response rate (CR)	To determine the anti-tumor effectivity of CB dualCAR-NK19/70	Up to 2 years
Secondary	Partial response rate (PR)	To determine the anti-tumor effectivity of CB dualCAR-NK19/70	Up to 2 years
Secondary	Progression free survival (PFS)	To determine the anti-tumor effectivity of CB dualCAR-NK19/70	Up to 2 years