A Phase I/II Multicentric Study to Determine the Safety and Efficacy of a Combination of Anti-CD3 & Anti-CD7 Ricin A Immunotoxins (T-Guard) for the Treatment of Steroid-resistant Acute Graft-versus-Host Disease.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Acute GVHD response rate
研究概览
简要总结
In this study, a combination of two antibodies both conjugated to a cell-killing toxin (so-called immunotoxins) will be evaluated. The antibodies are directed against T-cell antigens 'cluster of differentiation 3 antigen' (CD3) and CD7. Previous in vitro studies have demonstrated that this particular immunotoxin-combination, named T-Guard, acts synergistically in eliminating T cells with a preference for killing activated T-cells. In a subsequent clinical pilot-study, T-Guard has generated encouraging results when applied as third-line therapy for patients suffering form steroid-resistant acute Graft-versus-Host Disease (GVHD). Extensive biological and clinical responses could be noted in the absence of severe acute toxicities. Building on these results, the current study aims at evaluating the safety and efficacy of T-Guard for treating steroid-resistant GVHD when administered in an earlier phase of the disease process, i.e. as second-line instead of as third-line therapy.
详细描述
The experimental design is a bicentric non-controlled fixed-dose Phase I/II study. A total of 20 adult patients with acute steroid-resistant GVHD will be enrolled in a 12 months period. The treatment consists of a standard dose of 4 infusions T-Guard (4 mg/m2), given 48-hours apart over a 4-hour period. The intended follow-up period is 6 months.
The primary objective is to determine the efficacy of T-Guard, 4 weeks after the first infusion (Day 28), in inducing an objective clinical response in patients with acute GVHD refractory to standard first line corticosteroid therapy.
Secondary objectives are:
- To evaluate the overall safety and efficacy of T-Guard during the first 6 months after imitation of therapy;
- To determine the pharmacokinetic profile of T-Guard;
- To determine the immunogenicity of T-Guard.
Exploratory objectives are:
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 acute GVHD which is staged Grade II-IV according to the modified Glucksberg Criteria and progressing after 3 days, or not improving after 7 days, of methylprednisolone at a dose of 2 mg/kg per day.
- •Age ≥18 years.
- •Patients or an impartial witness (in case the patient is capable to provide verbal consent but not capable to sign the informed consent) should have given written informed consent.
排除标准
- •Patients receiving concomitant investigational therapeutics for acute GVHD, including investigational agents used for GVHD prophylaxis, at the time of enrollment.
- •Patients with signs or 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 15 g/l or less.
- •Patients having uncontrolled bacterial, viral or fungal infections, at the discretion of the investigator, at the start of therapy.
- •Patients with current signs or symptoms of active intrapulmonary disease.
- •Patients with known hypersensitivity to any of the components of the study drug.
- •Female patients who are pregnant, breast feeding, or, if sexually active, unwilling to use effective birth control for the duration of the study.
- •Male patients who are, if sexually active, unwilling to use effective birth control for 30 days after the last infusion.
- •Patients participating in a clinical trial with another investigational product within 30 days prior to providing informed consent.
- •Patients whose decision to participate might be unduly influenced by perceived expectation of gain or harm by participation, such as patients in detention due to official or legal order.
结局指标
主要结局
Acute GVHD response rate
时间窗: Day 28
The acute GVHD response rate at 4 weeks after the first injection of T-Guard (Day 28), being defined as as the fraction of patients showing a complete or partial response (CR or PR)
次要结局
- Anti-drug-antibodies(Pre-treatment, Day 14, Day 28, Day 90, and Day 180)
- Safety and tolerability of T-Guard(During 6 months after initiation of treatment)
- Incidence of chronic GVHD(During 6 months after initiation of therapy)
- Pharmacokinetic profile of T-Guard(Up to Day 9)
- Very good partial response rate(Day 28)
- Acute GVHD relapse rate(During 6 months after initiation of therapy)
- Overall survival and progression free survival(During 6 months after initiation of treatment)
- The occurrence of treatment-induced cytokine release(Day 1, 3, 5, and 7)