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

Sequential Treatment With 7x19 CAR-T After Umbilical Cord Blood Derived CD19 CARNK in Relapsed/Refractory B Cell Lymphoma

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

Study Overview

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

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 Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenbin Qian， Professor; Phone Number: +8613605801032; Email: qianwb@zju.edu.cn
• Study Contact Backup: Name: Hui Liu, Professor; Phone Number: 13819198629; Email: sylen@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • The Second Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Wenbin Qian, Professor; Phone Number: 13605801032; Email: qianwb@zju.edu.cn
      • Contact: Hui Liu, Doctor; Email: sylen@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: CD19-CAR-NK/T; Cord blood derived CD19 CARNK sequential Treatment with 7x19 CAR-T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLTs)	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	Up to 28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Wenbin Wenbin, Professor, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell
• Other Study ID Numbers: 2024 (0673)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No