Sequential Treatment of CD19 CARNK and 7x19 CAR-T in R/R B Cell Lymphoma

Phase 1

Recruiting

• Conditions: Primary Mediastinal B-cell Lymphoma (PMBCL); Mantle Cell Lymphoma (MCL); Diffuse Large B Cell Lymphoma( DLBCL)
• Interventions: Biological: CD19-CAR-NK/T

• Registration Number: NCT06464861
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

To study the safety and efficacy of cord blood-derived CD19 CAR-NK cells sequential with 7x19 CAR-T in relapse / refractory B cell lymphoma

Detailed Description

This is a single-center, open, single-arm clinical exploratory study to observe the safety and efficacy of cord blood derived CD19 CAR-NK cells sequential treatment with 7x19 CAR-T in relapse / refractory B cell lymphoma. This study consisted of two phases: phase I: CARNK cells preparation and infusion (Day0, dose of 2 x 10\^6 / kg). Phase II: 7x19 CAR-T cells preparation and infusion (Day7, dose 2×10\^6/kg).

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-06-13
• Study First Submitted QC: 2024-06-13
• Study First Posted: 2024-06-18
• Study Start: 2024-06-20
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-07
• Primary Completion: 2026-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. Age 18-75 years old, no gender limit;

2. 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:

   1. 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 ；
   2. Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors;
   3. Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment;

3. Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines;

4. At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;

5. The expected survival period is ≥12 weeks;

6. The puncture section of the tumor tissue was positive for CD19 expression;

7. ECOG score 0-2 points;

8. Sufficient organ function reserve:

   1. Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
   2. Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
   3. Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
   4. Glomerular filtration rate>50Ml/min
   5. Cardiac ejection fraction (EF) ≥50%;
   6. Under natural indoor air environment, basic oxygen saturation>92%

9. Allow a previous stem cell transplantation

10. 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;

11. Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;

12. Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial

13. Two tests for the new coronavirus or swine flu virus are negative.

Exclusion Criteria

1. Allergic to any of the components of cell products;
2. History of other tumors;
3. Acute GvHD or extensive chronic GvHD with grade II-IV (Glucksberg standard) in the past or are receiving anti-GVHD treatment;
4. Had received gene therapy within the past 3 months;
5. Active infections requiring treatment (except for simple urinary tract infections, bacterial pharyngitis); however, prophylactic antibiotics, antiviral and antifungal infection treatment are permitted;
6. Patents 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 dysfunction according to the New York Heart Association's cardiac function grading criteria;
8. Patients who received antitumor therapy earlier but did not recover from the toxicity (CTCAE 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia);
9. Subjects with a history of epilepsy or other central nervous system disorders;
10. Head-enhanced CT or MRI showing evidence of central nervous system lymphoma;
11. Lactating women who are unwilling to stop breastfeeding;
12. Any other factors that the investigator believes may increase the risk to the subject or interfere with the test results.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD19-CAR-NK/T	CD19-CAR-NK/T	All subjects were intravenously administrated with CAR-NK019 at day 0 with a dose of 2x10\^6/kg, and after 1 week will be infused with 7x19 CAR-T at the dose of 2x10\^6/kg

Primary Outcome Measures

Name	Time	Method
Incidence of dose limiting toxicity (DLTs)	Up to 28 days	To evaluate the safety and tolerability of cord blood-derived anti-CD19 CAR-NK Cell sequential with 7X19 CAR-T for B-cell Non-Hodgkin Lymphoma

Secondary Outcome Measures

Name	Time	Method
Complete response rate (CR)	Up to 2 years	To determine the CR rate of CB CD19 CAR-NK Cell sequential with 7X19 CAR-T for B-cell Non-Hodgkin Lymphoma
Duration of response (DOR)	Up to 2 years	To determine the DOR of CB CD19 CAR-NK Cell sequential with 7X19 CAR-T for B-cell Non-Hodgkin Lymphoma
Partial response rate (PR)	Up to 2 years	To determine the PR rate of CB CD19 CAR-NK Cell sequential with 7X19 CAR-T for B-cell Non-Hodgkin Lymphoma
Progression free survival (PFS)	Up to 2 years	To determine the anti-tumor efficacy of CB CD19 CAR-NK Cell sequential with 7X19 CAR-T for B-cell Non-Hodgkin Lymphoma
Overall survival (OS)	Up to 2 years	To determine the OS of CB CD19 CAR-NK Cell sequential with 7X19 CAR-T for B-cell Non-Hodgkin Lymphoma

Trial Locations

Locations (1)

the Second Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China