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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。评价复发或难治性惰性非霍奇金淋巴瘤(NHL)继发性患者对莫特沙芬(MGD)的临床有效率(完全缓解[CR]、未确认完全缓解[CRU]和部分缓解[PR])；-评估综合临床受益率(CR、CRU和PR，稳定疾病[SD])-评估无进展存活率-评估临床反应持续时间-评估MGD在此患者群体研究中的安全性和耐受性设计：一项基于Simon 2阶段设计的单臂开放标签II期研究，包括大约15名第1阶段患者和20名第2阶段患者，共35名患者。这项研究将包括长达6个28天的周期，或168天，对显示临床益处的患者进行长达1年的随访期。符合资格标准的患者将按顺序入选，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)每天服用6.0 mg/kg的MGD。将在第2、4和6周期的第21至28天评估患者的反应。将对患者进行跟踪，直到疾病进展、疾病复发，或在治疗完成后持续一年。进展性疾病(PD)或复发疾病(RD)患者将在任何时候被终止研究。持续时间：注册将在大约一年内完成。个别患者将参与这项研究，最长可达18个月。研究人群：患有难治性或复发性惰性NHL的成年人，东部合作肿瘤学小组(ECOG)的表现状态评分为0、1或2。终点：主要：-复发或难治性惰性NHL患者对MGD的临床应答率(CR、CRU、PR)次级：-临床受益率(CR、CRU、PR、SD)-无进展生存期-临床反应持续时间-MGD在治疗惰性NHL中的安全性和耐受性研究药物：MGD 6.0 mg/kg/d，在治疗A、治疗1至3天和治疗B、3天，每日静脉注射一次(Qd)从第15天到第17天，每个28天的周期，超过30分钟。就诊计划：首次接种后14天内进行筛查就诊。治疗随访：每28天周期的第1-3天(治疗A)和第15-17天(治疗B)每天1次，第2、4、6周期的第21-28天进行一次疗效评估。随访：CR、CRU、PR和SD患者：在完成第6周期的第一次MGD剂量后每隔60天进行一次，为期1年。PD、RD或在研究完成前终止的患者：在最后一次服用或终止MGD后30天。安全性随访：在最后一次服用MGD后至少30天。总体研究设计和计划：这项第二阶段试验将评估在大约35名复发或难治性惰性非霍奇金淋巴瘤患者中使用MGD所产生的临床反应率。试验设计基于SIMON两阶段临床试验设计，还将探讨这种治疗方法的24临床受益率、总体无进展存活率、临床反应持续时间和安全性。在整个治疗和安全随访期内，将监测患者的安全性(包括不良事件)。所有患者必须患有难治性或复发性惰性非霍奇金淋巴瘤，定义如下：-难治性疾病，定义为在最近的系统治疗期间疾病进展或对最近的系统治疗无反应(低于PR)--复发性疾病，定义为在最近的系统治疗后有反应的进行性疾病。符合资格标准的患者将按顺序入选，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)每天服用6.0 mg/kg的MGD。将在第2、4和6周期的第21至28天对患者的临床反应进行评估。未进展或复发的患者将继续进行研究，最多6个周期。患有(PD)或(RD)的患者将被从研究中终止。疾病没有进展和没有完成周期2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名患者中有不到两名患者出现应答(CR、CRU或PR)，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选，第二阶段的患者登记就会开始。在第二阶段，将按照与第一阶段相同的治疗方案和评估时间表，再招募20名患者进行治疗。