Clinical Study of Cord Blood-derived IL-10/IL-15 CD19-CAR NK in the Treatment of Refractory/Relapsed B-cell NHL

Обзор

To study the safety and effectiveness of cord blood-derived IL-10/IL-15 CD19-CAR NK in patients with B-cell non-Hodgkin's lymphoma

Подробное описание

This is an open, single-arm, single-dose, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CB IL-10/IL-15 CD19-CAR NK cells. 6-24 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). Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 30 patients will be enrolled in the dose-expansion trial. The primary endpoints are DLT and MTD; the second is the overall response rates (CR and PR), survival, and progression-free survival. Patients will be infused on day 0, day 3, and day 6， respectively.

Вмешательства

• Биопрепарат anti-CD19 IL10/IL15 CAR-NK
  Lentiviral vector-transducted cord blood-derived NK cells to express anti-CD19-IL10/IL-15 CAR

Первичные конечные точки

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

Вторичные конечные точки (6)

• Complete response rate (CR) [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]
• Overall survival (OS) [Срок оценки: Up to 2 years]
• Partial response rate (PR) [Срок оценки: Up to 2 years]
• Overall response rate (ORR) [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Volunteer to participate in this study and sign an informed consent form;
• 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:(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; (4) 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; 7, ECOG score 0-2 points;
• 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 Cardiac ejection fraction (EF) ≥50%; (5) 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 were negative.

Критерии исключения

• Those who have a history of allergies to any of the ingredients in cell products;
• History of other tumors;
• Previously presented with II-IV degree (Glucksberg criteria) acute GvHD or extensive chronic GvHD; or are receiving anti-GvHD treatment;
• Have received gene therapy in the past 3 months;
• Active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed;
• Hepatitis B (HBsAg positive, but HBV-DNA <103 is not an exclusion criterion) or hepatitis C virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including but not limited to people living with HIV;
• According to the New York Heart Association's Heart Function Classification Standard, it is classified as Grade III or Grade IV impaired subjects;
• Those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the CTCAE 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss);
• Subjects with a history of epilepsy or other central nervous system diseases; 10. Enhanced CT or MRI of the head showed evidence of central nervous system lymphoma;

11\. Have any other drugs that target CD19; 12. Women who are breastfeeding and unwilling to stop breastfeeding; 13. Any other situation that the investigator believes may increase the subject's risk 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: NCT06707259 · 2024（1369）

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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