Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBLeActivated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia
Phase 2 Clinical Trial of Infusing Haploidentical K562-mb15-41BBLeActivated and Expanded Natural Killer Cells as Consolidation Therapy for Pediatric Acute Myeloblastic Leukemia
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DOI：
10.1016/j.clml.2021.01.013
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发表时间：
2021-04-29
影响因子：
2.7
通讯作者：
Perez-Martinez, Antonio
中科院分区：
文献类型：
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作者：
Gomez Garcia, Lara Maria;Escudero, Adela;Perez-Martinez, Antonio
我们提出了一项开放、前瞻性、多中心、非随机的2期临床试验，将单倍体k562 -mb15- 41bble活化和扩增的自然杀伤（NKAE）细胞作为化疗后首次完全缓解的中度和中度急性髓系白血病患儿的巩固策略（NCT02763475）。本研究强调了招募患者进行细胞治疗试验的困难，但表明NKAE细胞输注是安全可行的。然而，由于纳入的患者数量少，生物替代标记物不足，我们无法得出疗效的结论。背景：急性髓系白血病（AML）约占儿科白血病病例的20%；30%的患者会复发。自然杀伤（NK）细胞的抗白血病特性及其在AML治疗中的安全性已被报道。我们提出了一项开放、前瞻性、多中心、非随机的2期临床试验，将单倍体k562 -mb15- 41bble活化和扩增NK （NKAE）细胞作为化疗后首次完全缓解的中度和中度风险AML儿童患者的巩固策略（NCT02763475）。患者和方法：在NKAE细胞输注前，患者接受淋巴消耗方案。在NKAE细胞输注后，患者给予低剂量(1 × 10（6)/IU/m(2)）皮下白介素-2。主要研究终点是AML无复发生存期。我们需要纳入35名患者来证明复发减少了50%。结果：7例患者（年龄中位数为7.4岁，范围为0.78 ~ 15.98岁）接受了13次NKAE细胞输注，中位数为36.44 × 10(6)个细胞/kg(范围为6.92 × 10（6) ~ 193.2 × 10(6)个细胞/kg）。我们观察到4例患者嵌合（中位嵌合率为0.065%，范围为0.05-0.27%）。中位随访33个月后，6例患者（85.7%）保持完全缓解。3年总生存率为83.3%(95%可信区间为68.1-98.5)，累计3年复发率为28.6%（95%可信区间为11.5-45.7）。由于患者招募较少，该研究被提前终止。结论：尽管NKAE细胞输注是安全可行的，但本研究强调了招募患者进行细胞治疗试验的困难。然而，由于纳入的患者数量少，生物标志物不足，我们无法得出关于疗效的结论。(C) 2021爱思唯尔公司版权所有。
We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBLeactivated and expanded natural killer (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk acute myeloid leukemia in first complete remission after chemotherapy (NCT02763475). This study emphasizes the difficulties in recruiting patients for cell therapy trials but showed that NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions on efficacy because of the small number of included patients and insufficient biological surrogate markers. Background: Acute myeloid leukemia (AML) accounts for approximately 20% of pediatric leukemia cases; 30% of these patients experience relapse. The antileukemia properties of natural killer (NK) cells and their safety profile have been reported in AML therapy. We proposed a phase 2, open, prospective, multicenter, nonrandomized clinical trial for the adoptive infusion of haploidentical K562-mb15-41BBLeactivated and expanded NK (NKAE) cells as a consolidation strategy for children with favorable and intermediate risk AML in first complete remission after chemotherapy (NCT02763475). Patients and Methods: Before the NKAE cell infusion, patients underwent a lymphodepleting regimen. After the NKAE cell infusion, patients were administered low doses (1 x 10(6)/IU/m(2)) of subcutaneous interleukin-2. The primary study endpoint was AML relapse-free survival. We needed to include 35 patients to demonstrate a 50% reduction in relapses. Results: Seven patients (median age, 7.4 years; range, 0.78-15.98 years) were administered 13 infusions of NKAE cells, with a median of 36.44 x 10(6) cells/kg (range, 6.92 x 10(6) to 193.2 x 10(6) cells/kg). We observed chimerism in 4 patients (median chimerism, 0.065%; range, 0.05-0.27%). After a median follow-up of 33 months, the disease of 6 patients (85.7%) remained in complete remission. The 3-year overall survival was 83.3% (95% confidence interval, 68.1-98.5), and the cumulative 3-year relapse rate was 28.6% (95% confidence interval, 11.5-45.7). The study was terminated early because of low patient recruitment. Conclusion: This study emphasizes the difficulties in recruiting patients for cell therapy trials, though NKAE cell infusion is safe and feasible. However, we cannot draw any conclusions regarding efficacy because of the small number of included patients and insufficient biological markers. (C) 2021 Elsevier Inc. All rights reserved.