NCT04128319终止3 期
An Open-Label, Single-Arm, Multicenter Study, of Combination Anti-CD3/CD7 Immunotoxin (T-Guard) for Steroid-Refractory Acute Graft-versus-Host Disease)
Xenikos24 个研究点 分布在 1 个国家目标入组 3 人开始时间: 2019年11月21日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 24
- 主要终点
- Complete Response (CR)
研究概览
简要总结
The study is designed as an open-label, single arm Phase III, multicenter trial to evaluate the efficacy and safety of T-Guard treatment in patients with Steroid-Refractory acute Graft versus Host Disease (SR-aGVHD).
详细描述
Allogeneic Hematopoietic Cell Transplantation (allo-HSCT) is a potent immunotherapy with curative potential for several hematological disorders. Improvements in survival following allo-HSCT have led to its increasing use, but the leading cause of non-relapse mortality (NRM) remains graft-versus-host-disease (GVHD. Despite recent advances in the understanding of transplantation immune tolerance, aGVHD is a frequent and major complication of allo-HSCT involving activation of donor T-lymphocytes, which ultimately causes host tissue damage. T-Guard has a rapid onset, preferential killing of activated T cells, and short half-life, leading to depletion of allo-reactive T cells and quick post-treatment reconstitution of the immune system.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be at least 12.0 years of age at the time of consent.
- •Patient has undergone first allo-HSCT from any donor source using bone marrow, peripheral blood stem cells, or cord blood. Recipients of nonmyeloablative, reduced intensity, and myeloablative conditioning regimens are eligible.
- •Patients diagnosed with SR-aGVHD after allo-HSCT. SR is defined as aGVHD that:
- •Progressed after 3 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day
- •No improvement after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day.
- •Patients with visceral (GI and/or liver) plus skin aGVHD at prednisone (or equivalent) initiation with improvement in skin GVHD without any improvement in visceral GVHD after 7 days of primary treatment with prednisone (or equivalent) of greater than or equal to 2mg/kg/day
- •Previously was treated with prednisone (or equivalent) of greater than or equal to 1mg/kg/day and aGVHD has developed in a previously uninvolved organ system
- •Progression and no improvement are defined in the protocol. Improvement or progression in organs is determined by comparing current organ staging to staging at initiation of prednisone (or equivalent) treatment. Staging is performed per MAGIC criteria.
- •Evidence of myeloid engraftment (e.g., absolute neutrophil count greater than or equal to 0.5 × 10^9/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed.
- •Patients or an impartial witness (in case the patient is capable of providing verbal consent but not capable of signing the informed consent form (ICF)) should have given written informed consent. For patients less than 18 years of age, a written informed consent of the parents or guardian and written assent of the patient will be obtained, per the local requirements.
排除标准
- •Patients who have been diagnosed with overlap syndrome, that is, with any concurrent features of cGVHD.
- •Patients requiring any of the following: mechanical ventilation, vasopressor support, or hemodialysis.
- •Patients who have received any systemic treatment, besides steroids, as upfront treatment of aGVHD OR as treatment for SR-aGVHD.
- •Patients who have severe hypoalbuminemia, with an albumin of less than or equal to 1 g/dl.
- •Patients who have a CK level of greater than 5 times the upper limit of normal.
- •Patients with uncontrolled infections. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- •Patients with evidence of relapsed, progressing or persistent malignancy.
- •Patients with evidence of minimal residual disease requiring withdrawal of systemic immune suppression
- •Patients with known hypersensitivity to any of the components murine monoclonal antibodies (mAb) or Recombinant Ricin Toxin A-chain (RTA).
- •Patients who have received more than one allo-HSCT.
- •Patients with known human immunodeficiency virus infection.
- •Female patients who are pregnant, breast feeding, or, if sexually active and of childbearing potential, unwilling to use effective birth control from start of treatment until 30 days after the last infusion of T-Guard.
- •Male patients who are, if sexually active and with a female partner of childbearing potential, unwilling to use effective birth control from start of treatment until 65 days after the last infusion of T-Guard.
- •Patients with any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the patient; or interfere with interpretation of study data.
- •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.
研究组 & 干预措施
T-Guard Treatment
Experimental
Patients will receive T-Guard for treatment of steroid-refractory acute GVHD.
干预措施: T-Guard (Drug)
结局指标
主要结局
Complete Response (CR)
时间窗: Day 28
Complete Response at Day 28 is defined as a score of 0 for the GVHD staging in all evaluable organs at the Day 28 visit along with freedom from additional systemic therapy for treatment of acute GVHD.
次要结局
- Relapse-free Survival(Days 180)
- Overall Survival (OS)(Day 30)
- Overall Response Rate (CR or Partial Response (PR))(Days 14, 28, and 56)
- Proportions of CR, PR, Mixed Response (MR), no Response (NR) and Progression(Days 7, 14, 28, and 56)
- Pharmacokinetics of T-Guard - CL(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
- Pharmacokinetics of T-Guard - t1/2(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
- Duration of Complete Response (DoCR)(Through Day 180)
- Incidence of Toxicities(initiation of T-Guard to 28 days post-last dose)
- Pharmacokinetics of T-Guard - Cinf(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
- Pharmacokinetics of T-Guard - AUC(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
- Non-Relapse Mortality (NRM)(Days 100 and 180)
- GVHD-free Survival(Days 90 and 180)
- Cumulative Incidence of Chronic GVHD(Day 180)
- Pharmacokinetics of T-Guard - Vc(Before each infusion & at the following post-infusion timepoints: 4, 5, 6, 8 & 24 hours for the 1st infusion; 4, 6 & 24 hours for the 2nd & 3rd infusions; 4, 6, 24 & 48 hours for the 4th infusion (infusions occur within the time frame of Day 0 to Day 14))
- Immunogenicity(Baseline, Days 7, 14, 28, 90, and 180)
- Cumulative Incidence of Disease Relapse/Progression(Day 180)
- Incidence of Systemic Infections(initiation of T-Guard to 28 days post-last dose)
研究者
研究点 (24)
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