A Clinical Study of CD19 CAR NK Cells for the Treatment of Relapsed/Refractory B-cell Related Autoimmune Diseases

Официальное название

An Exploratory Clinical Study of the Safety and Efficacy of CD19 Chimeric Antigen Receptor NK Cell Injections for the Treatment of Relapsed/Refractory B-cell Related Autoimmune Diseases

Обзор

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells (KN5501) in patients with relapsed/refractory B-cell related autoimmune diseases.15 patients are planned to be enrolled in the dose-escalation trial (6×10\^9 cells, 9×10\^9 cells). The primary objective of the study is to evaluation of the safety and feasibility of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The secondary objective is to evaluate the effectiveness of KN5501 for the treatment of relapsed/refractory B-cell related autoimmune diseases. The exploratory objective is to evaluate expansion, persistence and ability to deplete CD19 positive B cells of KN5501 in patients with relapsed/refractory B-cell related autoimmune diseases.

Вмешательства

• Препарат anti-CD19 CAR NK cells
  Patients will receive Fludarabine (30mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3, followed by Anti-CD19 CAR NK cells infusion.

Первичные конечные точки

• Incidence of Dose Limiting Toxicity (DLTs) [Срок оценки: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion]
• Treatment Emergent Adverse Events（TEAEs） [Срок оценки: within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion]

Вторичные конечные точки (2)

• Disease control rate of subjects [Срок оценки: 4, 12, 24, and 52 weeks after infusion]
• Remission rate of subjects [Срок оценки: 4, 12, 24, and 52 weeks after infusion]

Критерии участия

Критерии включения

• Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF) and are willing to follow and be able to complete all trial procedures
• Subjects disease status of enrolment: not complete response (CR) after standard treatment; moderately to severely active autoimmune diseases
• Age: ≥ 18 years old and ≤ 70 years old, male or female
• Subjects with estimated survival > 12 weeks
• Adequate organs function: Serum creatinine clearance meets relevant age/sex criteria,aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN)
• ECOG performance ≤ 2
• Left ventricular ejection fraction (LVEF) ≥ 45%
• Subjects have been treated with OCS in combination with an immunosuppressive or biologic agent for at least 2 weeks prior to enrollment

Критерии исключения

• Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions
• Subjects with one of the following genetic syndromes: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any of the known bone marrow failure syndromes
• Subjects with active or uncontrolled infections requiring parenteral antimicrobials; evidence of severe active viral or bacterial infections or uncontrolled systemic fungal infections
• Subjects with grade III or IV heart failure (NYHA classification)
• History of epilepsy or other central nervous system (CNS) diseases
• History of other primary malignant tumors except: cured non-melanoma skin cancer or primary cervical cancer; subjects with inactive tumors
• Subjects with more pronounced bleeding tendencies, such as gastrointestinal bleeding, coagulation disorders, and hypersplenism
• Subjects were treated with systemic corticosteroids concomitantly within 2 weeks prior to treatment
• Subjects with unstable angina, symptomatic congestive heart failure or myocardial infarction within the last 6 months
• Females who are pregnant, lactating, or planning a pregnancy within six months
• Subjects who have received other clinical trial treatment within 3 months
• Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome

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 · 2 центра

• Affiliated Hospital of Jiangsu University — Zhenjiang
• Jiangsu University Affiliated Hospital — Zhenjiang

Идентификаторы

NCT: NCT06318533 · 2023-11-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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