Phase I Study to Evaluate the Safety and Efficacy of NK Cell Therapy in Acute Myeloid Leukemia (AML).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
This is a phase 1, first-in-human (FIH), open-label, multicohort study to evaluate the safety, tolerability and preliminary efficacy of iPSC NK cells in patients with relapsed/refractory AML or AML Minimal Residual Disease (MRD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated informed consent form (ICF).
- •≥18 years old.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
- •Diagnosis of r/r AML (Cohort 1 and 2) or AML MRD (Cohort 3).
- •Cohort 1: Both CLL1 and CD33 expression are positive in AML blasts; Cohort 2: The expression of CD33 in AML blast is positive.
- •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.
排除标准
- •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.
研究组 & 干预措施
CD33/CLL1 dual CAR-NK cell
CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: CD33/CLL1 dual CAR-NK cell (Drug)
CD33/CLL1 dual CAR-NK cell
CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: Cyclophosphamid (Drug)
CD33/CLL1 dual CAR-NK cell
CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: Fludarabine (Drug)
CD33/CLL1 dual CAR-NK cell
CLL1/CD33 dual CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: Cytarabine (Drug)
CD33 CAR-NK cell
CD33 CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: Cyclophosphamid (Drug)
CD33 CAR-NK cell
CD33 CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: Fludarabine (Drug)
CD33 CAR-NK cell
CD33 CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: Cytarabine (Drug)
CD33 CAR-NK cell
CD33 CAR-NK cell therapy in Adult subjects with r/r AML
干预措施: CD33 CAR-NK cell (Drug)
super NK cell
super NK cell therapy in Adult subjects with AML MRD
干预措施: Cyclophosphamid (Drug)
super NK cell
super NK cell therapy in Adult subjects with AML MRD
干预措施: Fludarabine (Drug)
super NK cell
super NK cell therapy in Adult subjects with AML MRD
干预措施: Cytarabine (Drug)
super NK cell
super NK cell therapy in Adult subjects with AML MRD
干预措施: super NK cell (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: 28 Days from first dose of iPSC NK cell infusion
Incidence of subjects with Dose Limiting Toxicities within each dose level cohort
时间窗: 28 Days from first dose of iPSC NK cell infusion
次要结局
- Overall Response Rate(ORR)(Up to approximately 2 years after last dose of iPSC NK cell infusion)
- MRD negative rate(28 Days from first dose of iPSC NK cell infusion)
- Event-free survival(Up to approximately 2 years after last dose of iPSC NK cell infusion])
- Relapse-free survival(Up to approximately 2 years after last dose of iPSC NK cell infusion)
- Overall survival (OS)(Up to approximately 2 years after last dose of iPSC NK cell infusion)
- Determination of the pharmacokinetics (PK) of iPSC NK cells in peripheral blood(Up to approximately 2 years after last dose of iPSC NK cell infusion)