PHASE II TRIAL EXAMINING MULTIPLE IV INFUSIONS OF FOUR DOSES OF ABX C

II 期试验检查四剂 ABX C 的多次 IV 输注

• 批准号: 6265738
• 负责人: FRIEDRICH G SCHUENING
• 金额: $ 3.35万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265738
• 关键词: cell transplantation; clinical research; drug /agent; drug adverse effect; drug screening /evaluation; graft versus host disease; human subject; human therapy evaluation; immunopathology chemotherapy; intravenous administration; stem cells

This is a Phase II, multicenter, open label, dose escalation clinical trial examining multiple infusions of four doses of ABX-CBL in patients with steroid-resistant acute Graft Versus Host Disease (GVHD). Children and adults receiving a stem cell transplant within 100 days, with steroid resistant acute GVHD with a severity index of B, C, or D on the modified IBMTR Severity Scale may be eligible to participate in this study. A total of 48 patients, 12 per treatment cohort, will be enrolled in this study at six to ten clinical sites within the United States. Up to ten patients may be invited to participate at the University of Wisconsin. Patients will be infused with ABX-CBL daily for seven days (induction regimen) followed by a maintenance regimen of infusions two times per week for two weeks. Patients in all cohorts will receive up to eleven intravenous infusions of ABX-CBL. The study medication will be infused over two hours via a syringe pump. Safety evaluations will occur prior to advancing to the next cohort. The four cohorts are as follows: Cohort 1: 0.01 mg/kg; Cohort 2: 0.1 mg/kg; Cohort 3: 0.3 mg/kg; Cohort 4: 1.0 mg/kg. Patients will be followed for eight weeks (visits are weekly for four weeks followed by a visit four weeks later) for safety and clinical effect. Safety will be assessed by monitoring adverse events while on study as well as vital signs during the infusion of ABX-CBL, by frequent physical exams, laboratory studies including complete blood counts, T-cell subsets, serum chemistries, and urinalyses at regular intervals. Baseline CPK with isoenzymes will be obtained on all patients and patients who experience any infusion related adverse experiences will have repeat CPK with isoenzymes obtained. In addition, patients will be monitored for Human Anti Mouse Antibody (HAMA) response by ELISA. Clinical effect of ABX-CBL will be assessed by evaluating changes to the overall score of acute GVHD based upon a modified IBMTR Severity Index, time to response, duration of response, time and incidence of flare of acute GVHD, and length of hospitalization. Five patients in each cohort will be assigned to have pharmacokinetic blood samples for pK profile. The assignment to pK will be a combination of the first five patients in each cohort and the attempt to evenly distribute between males and females and adults and pediatrics. Patients who have received at least one infusion of ABX-CBL will be scheduled to participate in a long-term follow-up program to evaluate the long term safety of ABX-CBL and long term survival.

这是一项II期、多中心、开放标签、剂量递增的临床试验，研究了4种剂量的ABX-CBL多次输注治疗类固醇抵抗性急性移植物抗宿主病（GVHD）患者。在100天内接受干细胞移植的儿童和成人，患有类固醇抵抗性急性GVHD，严重程度指数在修改的IBMTR严重程度量表中为B、C或D，可能有资格参加本研究。共有48名患者，每个治疗队列12名，将在美国6至10个临床站点入组。威斯康星大学可能会邀请多达10名患者参加。患者将每天输注ABX-CBL 7天（诱导方案），然后是每周输注两次的维持方案，持续两周。所有队列的患者将接受最多11次静脉输注ABX-CBL。研究药物将通过注射泵注入两小时。安全性评估将在进入下一个队列之前进行。四个队列分别为：队列1:0.01 mg/kg；队列2:0.1 mg/kg；队列3:0.3 mg/kg；队列4:1.0 mg/kg。将对患者进行为期8周的随访（每周随访4周，四周后随访1周），以评估安全性和临床效果。安全性将通过监测研究期间的不良事件以及输注ABX-CBL期间的生命体征、频繁的身体检查、包括全血细胞计数、t细胞亚群、血清化学和定期尿液分析在内的实验室研究来评估。对所有患者进行基线CPK同工酶检测，对有输液相关不良反应的患者进行重复CPK同工酶检测。此外，将通过ELISA监测患者的人抗小鼠抗体（HAMA）反应。ABX-CBL的临床效果将通过评估急性GVHD的总体评分变化（基于改进的IBMTR严重指数）、反应时间、反应持续时间、急性GVHD发作时间和发生率、住院时间来评估。每组5名患者将被分配药代动力学血液样本进行pK分析。对pK的分配将是每个队列中前5名患者的组合，并试图在男性和女性、成人和儿科之间均匀分布。接受至少一次ABX-CBL输注的患者将被安排参加一个长期随访项目，以评估ABX-CBL的长期安全性和长期生存率。