Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates. Patients were treated with pralatrexate (10 to 25 mg/m2) and romidepsin (12 to 14 mg/m2) on 1 of 3 schedules: every week × 3 every 28 days, every week × 2 every 21 days, and every other week every 28 days. Treatment continued until progression, withdrawal of consent, or medical necessity. Twenty-nine patients were enrolled and evaluable for toxicity. Coadministration of pralatrexate and romidepsin was safe, well tolerated, with 3 DLTs across all schedules (grade 3 oral mucositis × 2; grade 4 sepsis × 1). The recommended phase 2 dose was defined as pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every other week. Twenty-three patients were evaluable for response. The overall response rate was 57% (13/23) across all patients and 71% (10/14) in PTCL. The phase 1 study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase 2 study in PTCL will determine the efficacy of the combination. This trial was registered at www.clinicaltrials.gov as #NCT01947140.

中文翻译：

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罗米地辛和普拉曲沙的 I 期研究显示在复发性和难治性 T 细胞淋巴瘤中具有显着活性

外周 T 细胞淋巴瘤 (PTCL) 是一组罕见的恶性肿瘤，其特征是化疗耐药和预后不良。Romidepsin 和pralatrexate 被美国食品和药物管理局批准用于复发/难治性PTCL 患者，反应率分别为25% 和29%。基于 PTCL 临床前模型的协同作用，我们启动了普拉曲沙联合罗米地辛治疗复发/难治性淋巴瘤患者的 1 期研究。这是一项针对普拉曲沙加罗米地辛的单一机构剂量递增研究，旨在确定剂量限制性毒性 (DLT)、最大耐受剂量、药代动力学特征和反应率。患者接受普拉曲沙（10 至 25 毫克/平方米）和罗米地辛（12 至 14 毫克/平方米）按以下 3 种方案之一进行治疗：每周 × 3 每 28 天，每周 × 2 每 21 天，每隔一周每 28 天一次。治疗一直持续到进展、撤回同意或医疗需要。招募了 29 名患者并对其毒性进行了评估。普拉曲沙和罗米地辛的联合给药是安全的，耐受性良好，在所有时间表中进行了 3 次 DLT（3 级口腔粘膜炎 × 2；4 级败血症 × 1）。推荐的 2 期剂量定义为每隔一周使用 pralatrexate 25 mg/m2 和 romidepsin 12 mg/m2。23 名患者可评估反应。所有患者的总体反应率为 57% (13/23)，PTCL 为 71% (10/14)。普拉曲沙加罗米地辛的 1 期研究在先前治疗过的 PTCL 患者中产生了高反应率。PTCL 的 2 期研究将确定组合的疗效。该试验在 www.clinicaltrials.gov 上注册为#NCT01947140。