NCT05744440招募中早期 1 期
Early Clinical Study of Allogenic NK Cells (JD002) in Combination With Chemotherapy in the Treatment of Relapsed or Refractory(r/r) Acute Myeloid Leukemia(AML) After Allo-HSCT
Xuzhou Medical University1 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2023年3月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicities
研究概览
简要总结
This is an open label, single-arm, Phase I study to evaluate the efficacy and safety of allogenic natural killer(NK) cells in subjects with refractory or relapsed AML after allogeneic hematopoietic stem cell transplantation(allo-HSCT). A leukapheresis procedure will be performed to manufacture NK cells. Prior to allogenic NK cells infusion subjects will receive chemotherapy with azacitidine.
详细描述
This open label, single-arm, Phase I study aims to evaluate the efficacy and safety of allogenic NK cells in subjects with refractory or relapsed AML after allo-HSCT. A leukapheresis procedure will be performed to manufacture NK cells. Prior to allogenic cells infusion subjects will receive chemotherapy with azacitidine. After infusion, the investigators will observe the characteristics of dose limited toxicity (DLT), and determine the maximum tolerable dose(MTD) and recommended phase 2 dose(rp2d) were confirmed. To provide basis for the dosage and treatment plan of cell products in follow-up clinical trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age18-75years old, no gender or race;
- •Expected survival is more than 3 months;
- •Eastern Cooperative Oncology Group (ECOG) score 0-2 points;
- •Diagnosed as AML in accordance with the criteria from Chinese guidelines for the diagnosis and treatment of adult AML (not acute promyelocytic leukemia (APL))(2021) and The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues;
- •Diagnosed as relapsed AML;
- •Measurable lesions meets at least one of the following requirements during screening: (1) Persistent positive MRD or relapse with positive minimal residual disease (MRD) in the bone marrow(BM); (2) Appearance of leukemic blasts in the peripheral blood; (3) ≥5% blasts in the BM; (4) extramedullary relapse;
- •Within 3 days prior to initial treatment, the organ functions meet the following requirements: (1) complete blood cell count: a. Absolute neutrophil counts ≥1.0×109/L and not treated with granulocyte colony stimulating factor(G-CSF) within 7 days; b.Hemoglobin ≥6g/dL(red blood cell; transfusion are permitted); c.Platelet ≥50×109/L(platelet transfusion are permitted); (2) Liver function: alanine transaminase (ALT)/ aspartate aminotransferase(AST) ≤ 3× times upper normal limit(ULN), total bilirubin ≤ 2 times ULN (direct bilirubin ≥ 1.5 times ULN is acceptable for subjects with Gilbert-Meulengracht syndrome); (3)Coagulation function: International standardized ratio (INR) or activated partial thrombin time (APTT) ≤1.5 times ULN; (4)Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30ml/min; (5)Corrected serum calcium ≤14mg/dL (≤3.5mmol/L) or free calcium ≥6.5mg/dL(≥1.6mmol/L); (6)Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%;
- •Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.
排除标准
- •Confirmed APL;
- •≥2 grade persistent nonhematologic toxicity of associated with prior treatment;
- •Patients with grade II-IV graft-versus-host disease (GVHD) requiring the use of immunosuppressive agents ;
- •Systemic steroid therapy exceeding the equivalent of ≥30mg/kg/day of prednisone within 48 hours prior to the first dose of study drug or other immunosuppressive therapies (except for topical and inhaled glucocorticoid therapy, or short-term prophylactic therapy with glucocorticoid) ;
- •Severe cardiovascular and cerebrovascular diseases, including: (1) Some cardiovascular and cerebrovascular diseases (such as congestive heart failure, acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism, etc.) occur within 6 months prior to the first dose of study drug; (2)New York Heart Association (NYHA) Class ≥3 or uncontrolled malignant arrhythmias; (3)The researchers assessed that the subjects with other cardiovascular and cerebrovascular diseases are not suitable for the study;
- •Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), syphilis infection, or active pulmonary tuberculosis;
- •History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
- •Previous or next organ transplant (except for HCT);
- •Women who are pregnant (urine/blood pregnancy test positive) or lactating;
- •Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 6 months after enrollment;
- •Any unstable condition potentially imperiling patient safety and compliance;
- •Known alcohol dependence or drug dependence;
- •According to the investigator's judgment, the patient has other unsuitable grouping conditions.
研究组 & 干预措施
allogenic NK cells
Experimental
Enrolled patients will receive prespecified dose of allogenic NK cells
干预措施: allogenic NK cells (Drug)
结局指标
主要结局
Dose-limiting toxicities
时间窗: 1 month
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Objective Response Rate(ORR)
时间窗: 3 months
Assessment of ORR (ORR = complete response(CR) + CRi（CR incomplete blood count recovery）+ PR(partial response)) at 3 months of treatment
次要结局
- Overall Survival(OS)(Month 6, 12, 18 and 24)
- Progression free survival(PFS) Assessment of PFS at month 6,12 Progression free survival(PFS)(Month 6,12)
研究者
Kai Lin Xu，MD
Principal Investigator
Xuzhou Medical University
研究点 (1)
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