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资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。评估临床缓解率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）的完全反应[CR]、未证实的完全反应[CRu]和部分反应[PR];- 评估综合临床受益率（CR、CRu和PR，疾病稳定[SD]）-评估无进展生存期-评估临床应答的持续时间-评价MGd在该患者人群中的安全性和耐受性一项基于Simon 2阶段设计的单臂、开放标签、II期研究，第1阶段入组约15例患者，第2阶段入组约20例患者，共计35例患者。 该研究将包括最多6个28天的周期，或168天，随访期长达1年的患者显示临床受益。符合合格性标准的患者将按顺序入组，并在每个28天周期的第1 - 3天（治疗A）和第15 - 17天（治疗B）每日接受6.0 mg/kg MGd治疗。将在第2、4和6周期的第21 - 28天评价患者的缓解。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。任何时间发生疾病进展（PD）或疾病复发（RD）的患者将终止研究。 持续时间：入组将在大约1年内完成。个体患者将参与研究长达18个月。 研究人群：患有难治性或复发性无痛性NHL的成人，东部肿瘤协作组（ECOG）体能状态评分为0、1或2。 终点：主要：- 临床反应率复发性或难治性惰性NHL患者中MGd的（CR、CRu、PR）次要：-临床获益率（CR、CRu、PR、SD）-无进展生存期-临床应答持续时间-MGd治疗惰性NHL的安全性和耐受性研究药物：在每个28天周期的第1 - 3天，治疗A和治疗B，第15 - 17天，每天一次（qd）静脉（IV）给予MGd 6.0 mg/kg/天，持续30分钟。 访视时间表：首次给药后14天内进行筛选访视。 治疗访视：在每个28天周期的第1 - 3天（治疗A）和第15 - 17天（治疗B）每日一次，在第2、4和6周期的第21 - 28天之间进行一次缓解评价。 随访访视：CR、CRu、PR和SD患者：完成第6周期的首次MGd给药后每60天一次，持续1年。PD、RD或在研究完成前终止研究的患者：末次MGd给药或终止研究后30天。 安全性随访：末次MGd给药完成后至少30天。 总体研究设计和计划：这项II期试验将在约35例复发性或难治性惰性NHL患者中评价使用MGd的临床应答率。试验设计基于Simon 2阶段临床试验设计，24还将探索该治疗疗法的临床获益率、总体无进展生存期、临床应答持续时间和安全性。在整个治疗和安全性随访期间，将监测患者的安全性（包括不良事件[AE]）。所有患者必须患有难治性或复发性惰性NHL，定义如下：-难治性疾病，定义为在最近的全身治疗期间疾病进展或对最近的全身治疗无反应（小于PR）-复发性疾病，定义为对最近的全身治疗有反应后疾病进展。 符合合格性标准的患者将按顺序入组，并在每个28天周期的第1 - 3天（治疗A）和第15 - 17天（治疗B）每日接受6.0 mg/kg MGd治疗。将在周期2、4和6的第21 - 28天评价患者的临床应答。疾病未进展或复发的患者将继续参加研究，最多持续6个周期。发生（PD）或（RD）的患者将终止研究。疾病未进展且未完成周期2治疗B和随访疾病评估的患者将被替换。如果第1阶段的15例患者中有不到2例出现缓解（CR、CRu或PR），则研究将不会进入第2阶段。否则，第2阶段的患者入组将在第1阶段的最后一例患者入组后开始。在第2阶段，将额外入组20例患者，并按照与第1阶段相同的治疗方案和评估时间表进行治疗。