Natural Killer(NK) Cell Therapy Targeting CLL1 in Acute Myeloid Leukemia

Официальное название

Clinical Study to Evaluate the Safety and Efficacy of iPSC NK Cells Targeting CLL1 in Patients With Relapsed/Refractory AML

Обзор

This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of CLL1 target CAR iPSC NK cells in patients with relapsed/refractory AML

Подробное описание

Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed disease in both pediatric and adultpatients. CLL-1 has attracted the researchers' attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 is an ideal target for AML.

Вмешательства

• Препарат CLL1 CAR-NK cell injection
  Drug: CLL1 NK cell therapy Drug: Cyclophosphamid Lympho-conditioning Agent Drug: Fludarabine Lympho-conditioning Agent Drug: VP-16 Lympho-conditioning Agent

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events [Срок оценки: 28 Days from first dose of iPSC NK cell infusion]
• Incidence of subjects with Dose Limiting Toxicities within each dose level cohort [Срок оценки: 28 Days from first dose of iPSC NK cell infusion]

Вторичные конечные точки (1)

• Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood [Срок оценки: Up to approximately 2 years after last dose of iPSC NK cell infusion]

Критерии участия

Критерии включения

• ≥18 years old.
• Confirmed diagnosis of r/r AML
• CLL1 expression is positive in AML blasts.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
• Adequate organ and marrow function, as defined below:

• Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft- Gault formula) ≥ 50 mL/min;
• Total bilirubin (TBIL) ≤ 2 x the ULN;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• Females of childbearing potential must have a negative serum pregnancy test.
• Donor specific antibody (DSA) is negative: MFI <= 2000.
• Provision of signed and dated informed consent form (ICF).

Критерии исключения

• Allergic to drug used in this study.
• Subjects received any antitumor therapy as follows, prior to first NK infusion:

• Systemic steroid therapy within 3 days (except physiological replacement therapy);
• Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less;
• Radiotherapy within 4 weeks;
• Donor lymphocyte infusion within 6 weeks;
• Intrathecal treatment within 1 week;
• CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months;
• History of allogeneic stem cell transplantation.
• Received the vaccine within 4 weeks prior to the first infusion and/or expected to require vaccination from the study period to 12 weeks after the last infusion.
• Active central nervous system Leukemia.
• Acute Promyelocytic Leukemia (APL).
• History of other malignant tumors, except for those who have achieved complete remission more than 5 years after radical treatment without any signs of recurrence.
• Active autoimmune diseases.
• History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc.
• Serious cardiovascular and cerebrovascular diseases:

• Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms;
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to first infusion;
• New York Heart Association (NYHA) class II or above congestive heart failure or left ventricular ejection fraction (LVEF) <50% in color Doppler echocardiography;
• Hypertension that cannot be controlled by drug.
• Active pulmonary infection; SpO2 ≤90%; Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease.
• Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
• History of substance abuse.
• Toxicity induced by previous therapy not recovered to ≤ grade 2(NCI-CTCAE v5.0).
• Large surgical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.
• Pregnant/breastfeeding women.
• Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject.

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

• Clinical research ethics committee of the first affiliated hospital, college of medicine, — Ханчжоу

Идентификаторы

NCT: NCT06027853 · QH-CLL1-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗