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

Official title

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

Overview

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).

Interventions

• Biological CD19-CAR-NK/T
  Cord blood derived CD19 CARNK sequential Treatment with 7x19 CAR-T

Primary outcome measures

• Incidence of dose limiting toxicity (DLTs) [Time frame: Up to 28 days]

Secondary outcome measures (5)

• Overall survival (OS) [Time frame: Up to 2 years]
• Progression free survival (PFS) [Time frame: Up to 2 years]
• Duration of response (DOR) [Time frame: Up to 2 years]
• Complete response rate (CR) [Time frame: Up to 2 years]
• Partial response rate (PR) [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• Age 18-75 years old, no gender limit;
• 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:

• 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 ；
• Refractory or relapsed MCL must be resistant to or intolerable to BTK inhibitors;
• Refractory or relapsed indolent B-cell NHL is the failure or recurrence of third-line treatment;
• Previous treatment must include CD20 monoclonal antibody treatment (unless the subject is CD20 negative) and anthracyclines;
• At least one measurable lesion with the longest diameter ≥ 1.5 cm exists;
• The expected survival period is ≥12 weeks;
• The puncture section of the tumor tissue was positive for CD19 expression;
• ECOG score 0-2 points;
• Sufficient organ function reserve:

• Alanine aminotransferase, aspartate aminotransferase ≤ 2.5× UNL (upper limit of normal value);
• Creatinine clearance rate (Cockcroft-Gault method) ≥60 mL/min;
• Serum total bilirubin and alkaline phosphatase ≤1.5× UNL;
• Glomerular filtration rate\>50Ml/min
• Cardiac ejection fraction (EF) ≥50%;
• Under natural indoor air environment, basic oxygen saturation\>92%
• Allow a previous stem cell transplantation
• 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;
• Allow patients who have previously received CAR-T cell therapy and have failed or relapsed after 3 months of evaluation;
• Female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial
• Two tests for the new coronavirus or swine flu virus are negative.

Exclusion criteria

• Allergic to any of the components of cell products;
• History of other tumors;
• Acute GvHD or extensive chronic GvHD with grade II-IV (Glucksberg standard) in the past or are receiving anti-GVHD treatment;
• Had received gene therapy within the past 3 months;
• Active infections requiring treatment (except for simple urinary tract infections, bacterial pharyngitis); however, prophylactic antibiotics, antiviral and antifungal infection treatment are permitted;
• 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;
• Subjects with Grade III or IV cardiac dysfunction according to the New York Heart Association\'s cardiac function grading criteria;
• 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);
• Subjects with a history of epilepsy or other central nervous system disorders;
• Head-enhanced CT or MRI showing evidence of central nervous system lymphoma;
• Lactating women who are unwilling to stop breastfeeding;
• Any other factors that the investigator believes may increase the risk to the subject or interfere with the test results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the Second Affiliated Hospital, College of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT06464861 · 2024 (0673)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗