Approval summary: Nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma
Approval summary: Nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma
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DOI：
10.1158/1078-0432.ccr-06-0606
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发表时间：
2006-09-15
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Cohen, Martin H.;Johnson, John R.;Pazdur, Richard
目的：描述导致 FDA 批准奈拉滨 (Arranon) 用于治疗 T 细胞急性淋巴细胞白血病/淋巴母细胞淋巴瘤的临床研究、化学制造和控制以及临床药理学和毒理学。 实验设计：对两项 2 期试验（一项在儿童患者中进行，另一项在成人患者中进行）进行了审查。静脉注射。儿科和成人研究中奈拉滨的剂量和给药方案分别为每天 650 mg/m(2)/d，持续 5 天，第 1、3 和 5 天分别为 1,500 mg/m(2)。每 21 天重复一次治疗。研究终点是完全缓解率 (CR) 和血液学或骨髓恢复不完全的 CR (CR*)。结果：儿科疗效人群由 39 名复发或对两种或多种诱导方案耐药的患者组成。 5 名 (13%) 患者观察到奈拉滨治疗 CR，9 名 (23%) 患者观察到 CR+CR*。成人有效人群包括 28 名患者。 5 名 (18%) 患者观察到奈拉滨治疗 CR，6 名 (21%) 患者观察到 CR+CR*。神经系统毒性对于儿童和成人患者来说都是剂量限制的。其他严重毒性包括儿科患者的实验室异常以及成人的胃肠道和肺部毒性。结论：2005年10月28日，美国食品和药物管理局加速批准奈拉滨用于治疗至少接受过两次既往治疗后的复发性或难治性T细胞急性淋巴细胞白血病/淋巴母细胞淋巴瘤患者。这种用途是基于 CR 的诱导。申请人将进行上市后临床试验以显示临床益处（例如，生存期延长）。
Purpose: To describe the clinical studies, chemistry manufacturing and controls, and clinical pharmacology and toxicology that led to Food and Drug Administration approval of nelarabine (Arranon) for the treatment of T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma.Experimental Design: Two phase 2 trials, one conducted in pediatric patients and the other in adult patients, were reviewed. The i.v. dose and schedule of nelarabine in the pediatric and adult studies was 650 mg/m(2)/d daily for 5 days and 1,500 mg/m(2) on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study end points were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*).Results: The pediatric efficacy population consisted of 39 patients who had relapsed or had been refractory to two or more induction regimens. CR to nelarabine treatment was observed in 5 (13%) patients and CR+CR* was observed in 9 (23%) patients. The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in 5 (18%) patients and CR+CR* was observed in 6 (21%) patients. Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults.Conclusions: On October 28, 2005, the Food and Drug Administration granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma after at least two prior regimens. This use is based on the induction of CRs. The applicant will conduct postmarketing clinical trials to show clinical benefit (e.g., survival prolongation).