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

这是一项II期、多中心、开放标签、剂量递增临床试验，检查了4种剂量的ABX-CBL多次输注治疗类固醇耐药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，如果患有类固醇耐药急性GVHD，且改良IBMTR严重程度量表上的严重程度指数为B、C或D，则可能有资格参加本研究。 本研究将在美国6 - 10家临床试验机构入组共计48例患者（每个治疗队列12例）。 威斯康星州大学可邀请多达10名患者参加。患者将每天输注ABX-CBL，持续7天（诱导方案），然后是每周输注2次的维持方案，持续2周。 所有队列中的患者将接受多达11次ABX-CBL静脉输注。 研究药物将在两小时内通过注射泵输注。 安全性评价将在进入下一个队列之前进行。四个队列如下：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周的安全性和临床效果随访（每周访视，持续4周，然后在4周后进行访视）。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，通过频繁的体格检查、实验室研究（包括全血细胞计数、T细胞亚群、血清化学和定期尿分析）来评估安全性。 将获得所有患者的基线CPK和同工酶，发生任何输注相关不良事件的患者将重复获得CPK和同工酶。 此外，将通过ELISA监测患者的人抗小鼠抗体（HAMA）应答。将通过基于改良IBMTR严重程度指数、至缓解时间、缓解持续时间、急性GVHD发作的时间和发生率以及住院时间评价急性GVHD总评分的变化来评估ABX-CBL的临床效果。每个队列中的5例患者将被分配用于采集PK谱的药代动力学血样。 PK分配将是每个队列中前5例患者的组合，并尝试在男性和女性以及成人和儿科之间均匀分布。接受过至少一次ABX-CBL输注的患者将被安排参加长期随访计划，以评价ABX-CBL的长期安全性和长期生存率。

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.