A Phase I Single-arm Clinical Study of Donor NK Cells Infusion Combined With Low-dose Interleukin-2 in the Treatment of Acute Myeloid Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Dose limiting toxicities (DLTs)
研究概览
简要总结
This is a single-centre, single-arm, open-label, early clinical study to evaluate the safety, tolerability and preliminary efficacy of donor NK cells injection combined with low-dose interleukin-2 in the treatment of acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
详细描述
This is a dose-escalation study of non-genetically modified natural killer cells derived from a healthy donor. The relapsed AML patients after allo-HSCT will receive donor NK cells injection s followed by low-dose interleukin-2. No graft-versus-host disease (GVHD) prevention will be conducted before or after infusion. Dose-limiting toxicity, incidence of adverse events, disease response and PK/PD will be detected post-infusion.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old,;
- •Expected survival period ≥ 3 months;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
- •The diagnosis of AML who received allo-HSCT, and met the following criteria:
- •A. Diagnostic criteria for relapsed AML: after complete remission (CR), leukemia cells reappeared in peripheral blood or blast cells in bone marrow ≥ 5% (except for other reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemia cell infiltration; B. Minimal Residual Disease (MRD) positive only or relapse: Patient is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment; C. Degree II and above acute graft-versus-host disease did not occur after transplantation; D. Available allogeneic hematopoietic stem cell transplant donors.
- •Adequate organ function: A. Liver function: ALT≤3×ULN, AST≤3×ULN, total bilirubin≤2×ULN; B. Coagulation function: international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤ 1.5×ULN; C. Renal function: serum creatinine≤1.5×ULN or creatinine clearance rate ≥30mL/min; D. Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 45%;
- •Women of child-bearing potential and all male participants must use effective methods of contraception for at least 12 months after infusion.;
- •Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.
排除标准
- •Central nervous system involved;
- •Patients who received the following anti-tumor therapies prior to infusion:
- •A. Systemic use of hormones within 3 days prior to infusion (except for patients with inhaled corticosteroids); B. Systemic anti-tumor therapy within 2 weeks or within 5 drug half-lives (whichever is shorter); C. Radiotherapy within 4 weeks; D. DLI within 6 weeks; E. Intrathecal injection within 1 week; F. Received CAR-T, CAR-NK or other modified cell therapy within 6 months;
- •Any active infection requiring systemic therapy by intravenous infusion within 14 days prior to the first dose of study drug, including: HBV, HCV, HIV, syphilis infection, or active pulmonary tuberculosis.
- •History of hypersensitivity reactions to murine protein-containing products, or macromolecular biopharmaceuticals such as antibodies or cytokines;
- •Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment;
- •Women who are pregnant (urine/blood pregnancy test positive) or lactating;
- •Suffering from a serious autoimmune disease or immunodeficiency disease;
- •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
NK cell treatment in AML replase after HSCT
The relapsed AML patients will receive donor NK cells injections for a total dose of twice per 2 weeks up to 3 dose levels (1.0×108 cells/dose，5.0×108 cells/dose，2.0×109 cells/dose), followed by low-dose interleukin-2 (1mIU ih, Qd) for 28 days.
干预措施: NK cell (Drug)
结局指标
主要结局
Dose limiting toxicities (DLTs)
时间窗: 1 month
Dose limiting toxicities (DLTs)
Treatment-related adverse events
时间窗: 1 month
Treatment-related adverse events
次要结局
- Complete response (CR)(3 months)
- Proportion of subjects with minimal-residual disease (MRD) negative response(3 months)
- Peak levels of donor NK cells (maximum concentration or Cmax)(3 months)
研究者
Yujun DONG
chief of department of hematology
Peking University First Hospital