An Open-Label, Dose-Finding Study of Vedolizumab IV for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 15
- 主要终点
- Percentage of Participants With Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28
研究概览
简要总结
The purpose of this study is to assess the initial activity, tolerability, safety and to identify a recommended dose and regimen of vedolizumab intravenous (IV) administered for treatment of steroid-refractory acute intestinal GvHD in participants who have undergone allo-HSCT.
详细描述
The drug being tested in this study is called vedolizumab. This study will look at the tolerability and effectiveness of vedolizumab IV in participants with acute intestinal GvHD who have received no systemic therapy for the treatment of acute GvHD (prophylaxis acceptable) other than corticosteroids.
The study enrolled 17 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:
- Vedolizumab 300 mg
- Vedolizumab 600 mg
All participants will be infused intravenously at the same time each day throughout the study. Vedolizumab IV will be administered on Days 1, 15, 43, 71, and 99. After approximately 10 participants are enrolled at each dose level and have data available from the Day 28 evaluation, safety, tolerability, efficacy, and pharmacokinetic (PK), results will be assessed for each dose level, and the appropriate dose for subsequent participants in the study will be determined.
This multi-center trial will be conducted in multiple countries. The overall time to participate in this study is 32 weeks. Participants will make multiple visits to the clinic after last dose of study drug for a follow-up assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Recipient of 1 allogeneic hematopoietic stem cell transplantation (allo-HSCT) but not more than 1 allo-HSCT.
- •Has primary steroid-refractory graft-versus-host disease (GvHD). Steroid-refractory disease is defined as worsening or no improvement in 5 to 7 days of treatment with methylprednisolone 2 milligram per kilogram (mg/kg) or equivalent or lack of a CR after 14 days of primary treatment with methylprednisolone 2 mg/kg or equivalent. Note that participants who develop intestinal GvHD while receiving systemic therapy for other GvHD are still eligible after 5 to 7 days, even if the intestinal GvHD has not been present for the entire duration. Participants who may have received an increase in their steroid dose treatment (example, increased methylprednisolone from 1 mg/kg to 2 mg/kg) before enrollment will be eligible, provided the participant has met the definition of steroid refractory above. Participants who develop toxicity on corticosteroids or who are otherwise medically unable to be dosed to this level, will also be eligible.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Evidence of myeloid engraftment defined by absolute neutrophil count greater than or equal to (>=) 0.5*109/liter (L) on 3 consecutive days.
排除标准
- •Presence of chronic GvHD at Screening (including acute-chronic overlap syndrome).
- •Relapse of underlying malignant disease after allo-HSCT.
- •Hyperacute GvHD defined as onset of GvHD within the first 15 days following hematopoietic stem cell infusion.
- •Received systemic agents other than corticosteroids for treatment of acute GvHD. GvHD prophylaxis agents (example, calcineurin inhibitors) may be continued.
- •Life expectancy of <3 weeks.
研究组 & 干预措施
Vedolizumab 300 mg
Vedolizumab 300 mg, intravenous (IV) infusion, once on Days 1, 15, 43, 71 and 99.
干预措施: Vedolizumab (Drug)
Vedolizumab 600 mg
Vedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Percentage of Participants With Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28
时间窗: Day 28
CR is defined as the resolution of all signs and symptoms of acute graft-versus-host-disease (GvHD). VGPR is defined as resolution of the signs and symptoms of the GvHD: 1) Skin: no rash, or residual erythematous rash involving \<25% of the body surface, without bullae (excluding residual faint erythema and hyperpigmentation). 2) Liver: total serum bilirubin concentration \<2 mg/dL or \<25% of baseline at enrollment. 3) Gut: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of 1 GvHD stage in 1 or more organs without progression in any organ.
Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Day 28
时间窗: From first dose up to Day 28
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
次要结局
- Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Months 6 and 12(Months 6 and 12)
- Percentage of Participants Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12(Months 6 and 12)
- Total Dose of Steroids Administered(From first dose of study drug up to Months 6 and 12)
- Percentage of Participants Who Died in the Absence of Primary Malignancy Relapse After Allo-HSCT at Month 6(Month 6)
- Number of Participants With Markedly Abnormal Laboratory Parameters Values(From Baseline up to last dose of study drug (Day 99))
- Number of Participants With Markedly Abnormal Vital Signs(From Baseline up to last dose of study drug (Day 99))
- Percentage of Participants With Acute GvHD Complete Response (CR) at Day 28(Day 28)
- Percentage of Participants With Intestinal Overall Response at Day 28(Day 28)
- Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)(From first dose of study drug to 18 weeks after last dose (Up to Week 32))
- Number of Participants Who Experienced Serious Adverse Events (SAEs) Through Week 32(From first dose of study drug to 18 weeks after last dose (Up to Week 32))
- Ctrough: Trough Serum Concentrations of Vedolizumab(Day 99 (pre-dose))