Chimeric Antigen Receptor-T (CAR-T) cell therapy is effective for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) but is not universally available. We developed a novel humanized CD19-directed CAR-T (HCAR19) approved for Phase 1/1b/2 trials. Patients aged 3–25 years were enrolled with r/r B-ALL and ineligible for allogeneic stem cell transplant. Lymphodepletion utilized standard-dose fludarabine and cyclophosphamide. A 3 + 3 design testing 3 dose-ranges was used to determine Phase-2 Dose (P2D): Dose-A, 1 × 106 HCAR19 cells/kg, Dose-B, 3–5 × 106/kg, and Dose-C, 10–15 × 106/kg. Primary endpoint was overall response rate (ORR) at day-30 on bone-marrow flow-cytometry. From May-2021 to September-2023 12 patients [median age-14 (range: 5–24) years] were enrolled with median bone marrow blasts 19.5% at screening. Cytokine release syndrome occurred in 10 (83%) patients, predominantly Grades 1–2, and Grade-2 immune-cell associated neurotoxicity (ICANS) in 1. All patients had Grade-3 cytopenia. ORR was 91.7% (11/12), complete response (CR) in 8 (66.7%) and partial response in 3 (25%). Seven of 8 CRs were at Dose-levels B and C, all of which were sustained till 12 months follow-up. Patients who received dose levels below 3 × 106/kg, or did not achieve CR, had early loss of response or rapid progression. HCAR19 demonstrated safety, manageable toxicity, and durable remissions. and P2D was determined as 5–10 × 106 HCAR19-cells/kg. The study is registered in the Clinical Trials Registry- India (CTRI/2021/05/033348 and CTRI/2023/03/050689).
嵌合抗原受体T细胞（CAR-T）疗法对复发/难治性B细胞急性淋巴细胞白血病（r/r B-ALL）有效，但尚未普及应用。我们开发了一种新型人源化CD19靶向CAR-T（HCAR19），已获批进行1/1b/2期临床试验。研究入组了3-25岁、不适合异基因造血干细胞移植的r/r B-ALL患者。淋巴细胞清除方案采用标准剂量氟达拉滨和环磷酰胺。采用3+3设计测试三个剂量范围以确定二期推荐剂量（P2D）：A剂量为1×10⁶ HCAR19细胞/千克，B剂量为3–5×10⁶/千克，C剂量为10–15×10⁶/千克。主要终点为第30天通过骨髓流式细胞术评估的总体缓解率（ORR）。2021年5月至2023年9月期间，共入组12例患者[中位年龄14岁（范围：5-24岁）]，筛查时骨髓原始细胞中位比例为19.5%。10例（83%）患者出现细胞因子释放综合征，主要为1-2级；1例出现2级免疫效应细胞相关神经毒性综合征（ICANS）。所有患者均发生3级血细胞减少。ORR为91.7%（11/12），其中完全缓解（CR）8例（66.7%），部分缓解3例（25%）。8例CR患者中有7例分布在B和C剂量组，且所有缓解均持续至12个月随访期。接受剂量低于3×10⁶/千克或未达到CR的患者，均出现早期缓解丧失或快速疾病进展。HCAR19展现出安全性良好、毒性可控且缓解持久的特点，二期推荐剂量确定为5–10×10⁶ HCAR19细胞/千克。本研究已在印度临床试验注册中心注册（CTRI/2021/05/033348和CTRI/2023/03/050689）。
肿瘤(癌症)患者之家