Abstract：
BACKGROUND: An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis.
METHODS: In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes.
RESULTS: We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 106 (n=3), 3 × 106 (n=3), and 10 × 106 (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths.
CONCLUSIONS: In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).
METHODS: In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes.
RESULTS: We enrolled nine patients with a median age of 57 years (range, 19 to 74) with an underlying diagnosis of aplastic anemia (n=4), myelofibrosis (n=4), or hypoplastic myelodysplasia (n=1). Patients had a median of three prior therapies for a bone marrow failure syndrome. Starting dose levels of CK0801 were 1 × 106 (n=3), 3 × 106 (n=3), and 10 × 106 (n=3) cells per kg of ideal body weight. No lymphodepletion was administered. CK0801 was administered in the outpatient setting with no infusion reactions, no grade 3 or 4 severe adverse reactions, and no dose-limiting toxicity. At 12 months, CK0801 induced objective responses in three of four patients with myelofibrosis (two had symptom response, one had anemia response, and one had stable disease) and three of four patients with aplastic anemia (three had partial response). Three of four transfusion-dependent patients at baseline achieved transfusion independence. Although the duration of observation was limited at 0.9 to 12 months, there were no observed increases in infections, no transformations to leukemia, and no deaths.
CONCLUSIONS: In previously treated patients, CK0801 demonstrated no dose-limiting toxicity and showed evidence of efficacy, providing proof of concept for targeting inflammation as a therapy for bone marrow failure. (Funded by Cellenkos Inc.; Clinicaltrials.gov number, NCT03773393.).
摘要：
背景：炎性骨髓微环境有助于获得性骨髓衰竭综合征。CK0801，一种同种异体T调节（Treg）细胞治疗产品，可能会中断这种持续的炎症循环并恢复造血。
方法：在CK0801Treg细胞的1期剂量递增研究中，我们纳入了对先前治疗反应欠佳的骨髓衰竭综合征患者,以确定该治疗对骨髓衰竭综合征的安全性和有效性.
结果：我们招募了9名患者，中位年龄为57岁（范围，19至74）的潜在诊断为再生障碍性贫血（n=4），骨髓纤维化（n=4），或增生性骨髓增生异常（n=1）。患者对骨髓衰竭综合征的先前疗法的中位数为三种。CK0801的起始剂量水平为1×106（n=3），3×106(n=3)，和每公斤理想体重10×106（n=3）个细胞。没有施用淋巴清除。CK0801在门诊使用，没有输液反应，无3级或4级严重不良反应,并且没有剂量限制性毒性。12个月时,CK0801在四名骨髓纤维化患者中的三名中诱导了客观反应（两名有症状反应，一个有贫血反应，1例疾病稳定）和4例再生障碍性贫血患者中的3例（3例部分缓解）。基线时，四名输血依赖患者中有三名实现了输血独立性。虽然观察时间限制在0.9至12个月，没有观察到感染增加，没有转化为白血病，也没有死亡。
结论：在以前接受过治疗的患者中，CK0801没有显示出剂量限制性毒性，并显示出疗效的证据，提供靶向炎症作为骨髓衰竭治疗的概念证明。（由CellenkosInc.资助；Clinicaltrials.gov编号，NCT03773393。).
方法：在CK0801Treg细胞的1期剂量递增研究中，我们纳入了对先前治疗反应欠佳的骨髓衰竭综合征患者,以确定该治疗对骨髓衰竭综合征的安全性和有效性.
结果：我们招募了9名患者，中位年龄为57岁（范围，19至74）的潜在诊断为再生障碍性贫血（n=4），骨髓纤维化（n=4），或增生性骨髓增生异常（n=1）。患者对骨髓衰竭综合征的先前疗法的中位数为三种。CK0801的起始剂量水平为1×106（n=3），3×106(n=3)，和每公斤理想体重10×106（n=3）个细胞。没有施用淋巴清除。CK0801在门诊使用，没有输液反应，无3级或4级严重不良反应,并且没有剂量限制性毒性。12个月时,CK0801在四名骨髓纤维化患者中的三名中诱导了客观反应（两名有症状反应，一个有贫血反应，1例疾病稳定）和4例再生障碍性贫血患者中的3例（3例部分缓解）。基线时，四名输血依赖患者中有三名实现了输血独立性。虽然观察时间限制在0.9至12个月，没有观察到感染增加，没有转化为白血病，也没有死亡。
结论：在以前接受过治疗的患者中，CK0801没有显示出剂量限制性毒性，并显示出疗效的证据，提供靶向炎症作为骨髓衰竭治疗的概念证明。（由CellenkosInc.资助；Clinicaltrials.gov编号，NCT03773393。).
