NCT03081780已完成1 期
Open Label Dose Escalation Trial of an Adaptive Natural Killer (NK) Cell Infusion (FATE-NK100) With Subcutaneous IL-2 in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This is a Phase I open-label dose escalation study of a single infusion of FATE-NK100 and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherapy (CY/FLU) in subjects with refractory or relapsed acute myelogenous leukemia (AML). FATE-NK100 is a natural killer (NK) cell product that is enriched for NK cells with an "adaptive", or human cytomegalovirus (CMV)-induced, phenotype. The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a related donor (HLA-haploidentical or better but not fully HLA-matched) that is seropositive for cytomegalovirus (CMV+), and enriched for adaptive NK cells by depletion of CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells followed by ex-vivo culture expansion.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 but ≤ 70 years of age
- •Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:
- •* Primary induction failure:
- •** De Novo AML: no CR after 2, 3 or 4 induction attempts with high dose chemotherapy
- •Secondary AML (from MDS or treatment related): no CR after 1, 2 or 3 cycles of high dose chemotherapy
- •Relapsed:
- •Not in CR after 1 or 2 cycles of standard re-induction therapy
- •Relapse diagnosed at the time of the 6 months post-HCT standard of care follow-up or later (i.e. based on bone marrow biopsy performed Day +170 or later) and without evidence of graft versus host disease (GVHD)
- •For patients > 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required.
- •Available HLA-matched or better but not fully HLA-matched (2/4 or 3/4 antigens) related donor (aged 18 to 75 years) with donor/recipient match based on a minimum of intermediate resolution DNA based Class I typing of the A and B locus who is CMV seropositive.
- •Karnofsky Performance Status ≥ 60%
- •Adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as:
- •Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m^2 per current institutional calculation formula
- •Hepatic: AST and ALT ≤ 3 x upper limit of institutional normal
- •Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if symptomatic or prior known impairment - must have pulmonary function >50% corrected DLCO and FEV1
- •Cardiac Function: LVEF ≥ 40% by echocardiography or MUGA
- •No symptomatic active conduction system abnormalities
- •Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to FATE-NK100 cell infusion (excluding preparative regimen premedications)
- •Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy
- •Voluntary written consent prior to the performance of any research related procedures
- •Arm Specific Inclusion Criteria
- •High-Risk aGVHD (ARM 1):
- •Pediatric or adult (ages 0-76 years) HCT recipients with high-risk acute GVHD, as determined either by the refined MN acute GVHD risk score [28]: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3) [31]. Patients in this arm must start treatment within the first 7 days after onset of high-risk aGVHD.
- •Steroid- Dependent aGVHD (ARM 2A):
- •Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid-dependent acute GVHD, defined as any one of the following: Flare of acute GVHD of at least grade II/IV severity within 8 weeks of tapering down or (off of) immunosuppression for acute GVHD, with the flare occurring on ≤0.5 mg/kg prednisone. This can include late-onset aGVHD and overlap syndrome.
- •Steroid-Refractory aGVHD (ARM 2B):
- •Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid refractory acute GVHD, defined as any one of the following:
- •No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
- •Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
- •Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent
- •Flare of acute GVHD of at least grade II/IV severity while on steroids at a dose >0.5/mg/kg/day. This can include late-onset aGVHD and overlap syndrome.
排除标准
- •Myocardial Infraction (MI) within the previous 6 months
- •Acute leukemias of ambiguous lineage
- •Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test at screening
- •History of or known active CNS involvement with AML
- •Active autoimmune disease requiring systemic immunosuppressive therapy
- •History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible)
- •New or progressive pulmonary infiltrates on screening chest X-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
- •Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed
- •Received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: 3 months
Maximum FATE-NK100 dose which could be given to 3 participants such that not more than 1 participant experienced a DLT.
次要结局
- Clinical activity by CR/CRp leukemia clearance(Day +42)
- In vivo expansion of NK cells(Day +14)
- Leukemia free survival (LFS)(1 year)
- Clinical activity by CR/CRp neutrophil recovery(Day +42)
- Minimal residual disease (MRD) by flow cytometry(up to Day 28)
- Overall survival (OS)(1 year)
- Treatment Related Mortality (TRM)(6 months)
- Minimal residual disease (MRD) by bone marrow morphology(up to Day 28)
研究者
研究点 (2)
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