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

Официальное название

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

Обзор

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

Подробное описание

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).

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (5)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Идентификаторы

NCT: NCT06464861 · 2024 (0673)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗