A Phase I/II Multicentric Study to Determine the Safety and Efficacy of a Combination of Anti-CD3 & Anti-CD7 Ricin A Immunotoxins for the Treatment of Steroid-Resistant Acute Graft-Versus-Host Disease
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Henogen
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- The acute GVHD response rate on study Day 29
研究概览
简要总结
In this study, a combination of two T-cell directed antibodies both conjugated to a cell-killing toxin will be evaluated. Previous in vitro studies have demonstrated that this so-called immunotoxin-combination (IT-combination) acts synergistically in eliminating T cells. In a subsequent clinical pilot-study, the IT-combination has generated encouraging results when applied as third line therapy. Extensive biological and clinical responses could be noted in the absence of severe acute toxicities. Building on this experience, the current study aims at evaluating the characteristics of the IT-combination when administered in an earlier phase of the disease, i.e. as second line instead of as third line therapy.
详细描述
"The experimental design is a non-controlled multicentric fixed-dose Phase I/II study. A total of 12 evaluable patients will be enrolled in 4 transplant centers throughout the Netherlands, in a 9 to 12 months period. The treatment consists of a standard dose of 4 infusions IT-combination (4 mg/m2), given 48-hours apart over a 4-hour period.
The intended follow-up period is 12 months. The patient will also be asked to participate in additional research aiming at determining the presence and evolution of biomarkers suggestive for the extent to which the IT-combination 'resets the T-cell compartment, induces clinical tolerance, and/or enhances the risk of over-immunosuppression."
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients suffering from severe acute GVHD (Grade II-IV) progressing after 3 days, or non-improving after 5 days, of prednisolone at 2 mg/kg a day.
- •Age ≥ 18 years.
- •Patients or their guardians should have given written informed consent using forms approved by the Institutional Review Board.
排除标准
- •Patients receiving concomitant investigational therapeutics/prophylaxis for acute GVHD at the time of enrollment.
- •Patients with histological signs/symptoms suggestive of chronic GVHD.
- •Patients requiring mechanical ventilation, requiring vasopressor support, requiring hemodialysis, having serum creatinine > 266 μmol/l (> 3 mg/dl), or having a serum albumin level of 20 g/l or less.
- •Patients having uncontrolled bacterial, viral or fungal infections at the start of therapy.
- •Patients with current evidence of active intrapulmonary disease.
- •Patients with known hypersensitivity to any of the components of the study drug (murine mAb or RTA).
- •Patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study.
结局指标
主要结局
The acute GVHD response rate on study Day 29
时间窗: Day 29
次要结局
- The safety and tolerability of the IT-combination, as determined by the number and intensity of adverse and serious adverse events during 12 months(12 months)
- The acute GVHD relapse rate(12 months)
- The incidence of chronic GVHD during 12 months(12 months)
- The overall survival and progression free survival during 12 months(12 months)
- The kinetics of treatment-induced T cell and Natural Killer (NK) cell depletion(12 months)
- The pharmacokinetic profile of the IT-combination(day 9)
- The occurrence and extent of humoral responses against the IT-combination(12 months)
- The occurrence of any treatment-induced cytokine release(day 7)