TRIAL OF MOTEXAFIN GADOLINIUM (MGD) IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA

莫替沙芬钆 (MGD) 在非霍奇金淋巴瘤患者中的试验

• 批准号: 7375269
• 负责人: RAJ ADVANI
• 金额: $ 1.51万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375269
• 关键词: TRIAL; MOTEXAFIN; GADOLINIUM; MGD; PATIENTS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To assess the clinical response rate (complete response [CR], unconfirmed complete response [CRu], and partial response [PR]), to Motexafin Gadolinium (MGd) in patients with relapsed or refractory indolent non-Hodgkin's Lymphoma (NHL) Secondary; -To assess the combined clinical benefit rate (CR, CRu, and PR, stable disease [SD]) -To assess progression-free survival -To assess duration of clinical response -To evaluate the safety and tolerability of MGd in this patient population Study Design: A one-arm, open-label, Phase II study based on a Simon 2-Stage design enrolling approximately 15 patients in Stage 1 and 20 patients in Stage 2, for a total of 35 patients. The study will consist of up to six 28-day cycles, or 168 days, with a follow-up period of up to 1 yr for patients showing clinical benefit. Patients who meet the eligibility criteria will be enrolled sequentially and treated daily with 6.0 mg/kg MGd on days 1 through 3 (Treatment A) and days 15 through 17 (Treatment B) of each 28-day cycle. Patients will be evaluated for response between days 21 and 28 of cycles 2, 4, and 6. Patients will be followed until disease progression, disease relapse, or for one year after treatment is completed. Patients with progressive disease (PD) or relapsed disease (RD) at any time will be terminated from the study. Duration: Enrollment will be completed in approximately 1 yr. Individual patients will participate in the study for up to 18 months. Study Population: Adults with refractory or relapsed indolent NHL with Eastern Cooperative Oncology Group (ECOG) performance status scores of 0, 1, or 2. Endpoints: Primary: -Clinical response rate (CR, CRu, PR) to MGd in patients with relapsed or refractory indolent NHL Secondary: -Clinical benefit rate (CR, CRu, PR, SD) -Progression-free survival -Duration of clinical response -Safety and tolerability of MGd in the treatment of indolent NHL Investigational Drug: MGd 6.0 mg/kg/day administered intravenously (IV) once a day (q d) on Treatment A, Days 1 through 3, and Treatment B, days 15 through 17, of each 28-day cycle, over 30 minutes. Visit Schedule: Screening visit within 14 days of first dose. Treatment visits: Once daily on Days 1 through 3 (Treatment A) and Days 15 through 17 (Treatment B) of each 28-day cycle and once for response evaluation between days 21 and 28 of Cycles 2, 4, and 6. Follow-up visits: Patients with CR, CRu, PR, and SD: Every 60 days after completion of the first MGd dose of Cycle 6 for 1 yr. Patients with PD, RD, or who terminate before study completion: 30 days after the last MGd dose or termination. Safety follow-up: At least 30 days after completion of the last MGd dose. Overall Study Design and Plan: This Phase II trial will evaluate the clinical response rate resulting from the use of MGd in approximately 35 patients with relapsed or refractory indolent NHL. The trial design is based on a Simon 2-stage clinical trial design, 24 Clinical benefit rate, overall progression-free survival, clinical response duration, and safety of this treatment therapy will also be explored. Patients will be monitored for safety (including adverse events [AEs]) throughout the treatment and safety follow-up periods. All patients must have refractory or relapsed indolent NHL as defined by the following: -Refractory disease, defined as disease progression during most recent systemic therapy or no response (less than PR) to most recent systemic therapy -Relapsed disease, defined as progressive disease after having responded to most recent systemic therapy. Patients who meet the eligibility criteria will be enrolled sequentially and treated daily with 6.0 mg/kg MGd on days 1 through 3 (Treatment A) and days 15 through 17 (Treatment B) of each 28-day cycle. Patients will be evaluated for clinical response between days 21 and 28 of Cycles 2, 4, and 6. Patients whose disease has not progressed or relapsed will continue on the study for a maximum of six cycles. Patients with (PD) or (RD) will be terminated from the study. Patients whose disease does not progress and who do not complete Cycle 2 Treatment B and follow-up disease assessments will be replaced. If fewer than two of the 15 patients in Stage 1 exhibit response (CR, CRu, or PR), the study will not proceed to Stage 2. Otherwise, patient enrollment for Stage 2 will begin as soon as the last patient in Stage 1 has been enrolled. In Stage 2, an additional 20 patients will be enrolled and treated following the same treatment regimen and assessment schedule as in Stage 1.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。评估复发性或难治性惰性非霍奇金淋巴瘤（NHL）继发性患者对莫替沙芬钆（MGd）的临床缓解率（完全缓解[CR]、未经证实的完全缓解[CRu]和部分缓解[PR]）； - 评估综合临床获益率（CR、CRu 和 PR、疾病稳定 [SD]） - 评估无进展生存期 - 评估临床反应持续时间 - 评估 MGd 在该患者群体中的安全性和耐受性 研究设计：一项基于 Simon 2 阶段设计的单臂、开放标签 II 期研究，招募约 15 名第一阶段患者和 20 名第二阶段患者，总共 35 名患者。 该研究将包括最多六个 28 天的周期，即 168 天，对显示临床获益的患者进行长达 1 年的随访。符合资格标准的患者将按顺序入组，并在每个 28 天周期的第 1 至 3 天（治疗 A）和第 15 至 17 天（治疗 B）每天接受 6.0 mg/kg MGd 治疗。将在第 2、4 和 6 个周期的第 21 天至 28 天之间评估患者的反应。将对患者进行随访，直至疾病进展、疾病复发或治疗完成后一年。任何时候患有疾病进展（PD）或疾病复发（RD）的患者将被终止研究。 持续时间：注册将在大约一年内完成。个别患者将参与长达 18 个月的研究。 研究人群：患有难治性或复发性惰性 NHL 的成人，且东部肿瘤合作组 (ECOG) 体力状态评分为 0、1 或 2。 临床反应 - MGd 在治疗惰性 NHL 试验药物中的安全性和耐受性：MGd 6.0 mg/kg/天，在治疗 A（第 1 至 3 天）和治疗 B（第 15 至 17 天）静脉内（IV）每天一次（q d）给药，每个 28 天周期，持续 30 分钟。 访视时间表：首次给药后 14 天内进行筛查访视。 治疗访视：每个 28 天周期的第 1 至 3 天（治疗 A）和第 15 至 17 天（治疗 B）每天一次，并在第 2、4 和 6 周期的第 21 至 28 天期间进行一次疗效评估。随访：CR、CRu、PR 和 SD 患者：第 6 周期第一次 MGd 剂量完成后每 60 天一次，持续 1 年。 PD、RD 患者或研究完成前终止的患者：最后一次 MGd 剂量或终止后 30 天。 安全随访：完成最后一剂 MGd 后至少 30 天。 总体研究设计和计划：这项 II 期试验将评估约 35 名复发或难治性惰性 NHL 患者使用 MGd 所产生的临床反应率。该试验设计基于西蒙2阶段临床试验设计，24还将探讨该治疗疗法的临床受益率、总体无进展生存期、临床反应持续时间和安全性。在整个治疗和安全随访期间，将监测患者的安全性（包括不良事件 [AE]）。所有患者都必须患有难治性或复发性惰性 NHL，定义如下： - 难治性疾病，定义为最近一次全身治疗期间疾病进展或对最近一次全身治疗无反应（低于 PR） - 复发性疾病，定义为对最近一次全身治疗有反应后疾病进展。 符合资格标准的患者将按顺序入组，并在每个 28 天周期的第 1 至 3 天（治疗 A）和第 15 至 17 天（治疗 B）每天接受 6.0 mg/kg MGd 治疗。将在第 2、4 和 6 个周期的第 21 天至 28 天之间评估患者的临床反应。疾病未进展或复发的患者将继续最多六个周期的研究。患有（PD）或（RD）的患者将被终止研究。疾病未进展且未完成第 2 周期治疗 B 和后续疾病评估的患者将被替换。如果第一阶段的 15 名患者中只有不到两人表现出缓解（CR、CRu 或 PR），则研究将不会进入第二阶段。否则，一旦第一阶段的最后一名患者入组，第二阶段的患者入组将立即开始。在第二阶段，将另外招募 20 名患者，并按照与第一阶段相同的治疗方案和评估时间表进行治疗。