肿瘤细胞治疗研究
英文原题：CD5-deleted Chimeric Antigen Receptor Cells (Senza5 CART5) for T Cell Non-Hodgkin Lymphoma (NHL)
这是一项 I 期注册临床试验，评估细胞治疗用于非霍奇金淋巴瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 30 例。试验地点：美国 · 纽约、费城（共 2 个中心）。登记号：NCT06420089。
不限性别 · ≥ 18 Years
入选标准 1. 组织学或细胞学确诊为复发/难治性（r/r）CD5阳性淋巴结型外周T细胞淋巴瘤，例如外周T细胞淋巴瘤非特指型（PTCL-NOS）、具有滤泡辅助性T细胞（TFH）表型的淋巴结型T细胞淋巴瘤（包括滤泡性T细胞淋巴瘤、血管免疫母细胞性淋巴瘤）或间变性大细胞淋巴瘤；或其他非白血病型CD5阳性侵袭性成熟T细胞淋巴瘤，例如肠病相关T细胞淋巴瘤、单形性亲上皮性肠道T细胞淋巴瘤、转化型蕈样肉芽肿、原发性皮肤侵袭性亲表皮CD8阳性细胞毒性T细胞淋巴瘤、原发性皮肤γδT细胞淋巴瘤或皮下脂膜炎样T细胞淋巴瘤。 2. 最近一次活检中，流式细胞术或免疫组织化学（IHC）检测显示恶性细胞CD5表达≥50%。 3. 淋巴瘤既往至少接受过一线全身治疗；间变性大细胞淋巴瘤（ALCL）患者须既往接受过维布妥昔单抗治疗，存在禁忌证者除外。 4. 有可评估疾病，定义为至少有一个可测量病灶：CT或PET扫描至少一个维度可测量，最长径≥1.5 cm；或存在骨/骨髓受累或皮肤受累。 5. 外周血流式细胞术未检出循环CD5阳性恶性细胞。 排除标准 1. 妊娠或哺乳期女性。 2. HIV感染。 3. 同时使用全身性类固醇或免疫抑制药物。 4. 存在任何未控制的活动性疾病，导致无法按方案参加研究。 5. 有免疫缺陷病史。 6. 既往接受过嵌合抗原受体治疗（CAR-T）；自体或同基因造血细胞移植距细胞输注不足100天；或既往接受过异基因造血细胞移植。 7. 存在活动性和/或全身性炎症性疾病或自身免疫病。 8. 有提示CNS活动性受累的体征或症状。 9. 有视神经炎或其他影响中枢神经系统的免疫性/炎症性疾病病史或既往诊断，且与淋巴瘤或既往淋巴瘤治疗无关。 10. 有临床表现的心律失常，或经药物治疗仍不稳定的心律失常。 11. 首次治疗给药前2周内正在参加或曾参加试验药物研究，或使用试验器械。 12. 研究第1天前4周内接受过单克隆抗体治疗。 13. 既往使用过阿仑单抗。 14. 研究第1天前2周内接受过化疗、靶向小分子治疗或放射治疗。 15. 存在需全身治疗的未控制活动性感染。 16. 外周血流式细胞术检出循环CD5阳性恶性细胞。 17. 存在活动性和/或全身性炎症性疾病或自身免疫病。
Inclusion Criteria: 1. Histologically or cytologically confirmed relapsed or refractory (r/r) CD5-positive nodal peripheral T-cell lymphoma (such as peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), nodal T-cell lymphomas with T-follicular helper (TFH) phenotype, including follicular T cell lymphoma, angioimmunoblastic lymphoma, or anaplastic large cell lymphoma) or other non-leukemic CD5+ aggressive mature T cell lymphomas (such as enteropathy-associated T cell lymphoma, monomorphic epitheliotropic intestinal T cell lymphoma, transformed mycosis fungoides, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, primary cutaneous insert gamma delta symbols lymphoma, or subcutaneous panniculitis like T cell lymphoma). 2. ≥50% expression of CD5 on flow cytometry or IHC on malignant cells on the most recent biopsy 3. Must have received at least one line of prior systemic therapy for their lymphoma; participants with anaplastic large cell lymphoma (ALCL) must have received prior brentuximab unless there was a contraindication to brentuximab. 4. Evaluable disease defined by at least one lesion that can be measured in least 1 dimension and measures at least 1.5 cm in its longest dimension by CT or PET scan, or bone/bone marrow involvement, or skin involvement. 5. No circulating CD5+ malignant cells identified by peripheral blood flow cytometry must be present. Exclusion Criteria: 1. Pregnant or lactating (nursing) women. 2. HIV infection. 3. Concurrent use of systemic steroids or immunosuppressant medications. 4. Any uncontrolled active medical disorder that would preclude participation as outlined. 5. History of immunodeficiency. 6. History of prior chimeric antigen receptor therapy (CAR T), autologous or syngeneic HCT \<100 days from transplant at the time of cell infusion or previous allo-HCT. 7. Active and/or systemic inflammatory or autoimmune diseases. 8. Signs or symptoms indicative of active CNS involvement. 9. Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to lymphoma or previous lymphoma treatment. 10. Clinically apparent arrhythmia, or arrhythmias that are not stable on medical management 11. Current participation in or prior participation in a study of an investigational agent or using an investigational device within 2 weeks of the first dose of treatment. 12. Prior monoclonal antibody therapy within 4 weeks prior to study Day 1 13. Prior use of alemtuzumab 14. Prior chemotherapy targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 15. Uncontrolled active infection requiring systemic therapy. 16. Circulating CD5+ malignant cells identified by peripheral blood flow cytometry present. 17. Active and/or systemic inflammatory or autoimmune diseases.
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Determine the recommended phase 2 dose (RP2D) of Senza5 CART5 cells · Measure the occurrence of Dose Limiting Toxicity events of each dose level per arm · 12 months
次要终点：Determine the safety of Senza5 CART5 cells；Determine the maximum tolerated dose (MTD)；Determine the manufacturing feasibility of Senza5 CART5；Determine efficacy of Senza5 CART5；Determine efficacy of Senza5 CART5；Determine efficacy of Senza5 CART5；Determine efficacy of Senza5 CART5；Determine efficacy of Senza5 CART5
采用标准淋巴清除方案，共4个治疗组：静脉给予氟达拉滨25 mg/m²，连续3天；静脉给予环磷酰胺250 mg/m²，连续3天。
用于已处于淋巴细胞减少状态的患者，并按相应剂量水平接受治疗。
这是一项开放标签I期研究，旨在确定Senza5 CART5细胞治疗复发/难治性CD5阳性淋巴结型T细胞非霍奇金淋巴瘤（NHL）的安全性和推荐II期剂量（RP2D）。RP2D将根据Senza5 CART5细胞的安全性、耐受性、药代动力学及初步疗效确定。本试验采用贝叶斯最优区间（BOIN）设计，评估最多5个剂量水平；每个队列纳入3名患者，以评估安全性并确定达到治疗水平的剂量，从而确定单次静脉输注Senza5 CART5细胞的RP2D。
This is an open-label phase I study to determine the safety and recommended phase 2 dose (RP2D) of Senza5 CART5 cells in patients with relapsed or refractory CD5 positive nodal T cell NHL. RP2D will be based on the safety, tolerability, pharmacokinetics, and preliminary efficacy of Senza5 CART5 cells. This trial will evaluate up to 5 dose levels using the Bayesian Optimal Interval (BOIN) design enrolling 3 patients in each cohort to assess safety and achieve therapeutic levels so that the RP2D of Senza5 CART5 cells given as a single IV infusion can be determined.
MEMBER ACCOUNT
登录成功会直接打开下一页。
