An Open-Label, Dose-Finding Study of Vedolizumab IV Plus Standard of Care for Graft-Versus-Host Disease (GvHD) Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to assess the initial tolerability, safety and recommended phase 2 dose of vedolizumab intravenous (IV) administered for GvHD prophylaxis along with standard GvHD prophylaxis therapy (in participants undergoing allogeneic hematopoietic stem cell transplantation [allo-HSCT]).
详细描述
The drug being tested in this study is called Vedolizumab. Vedolizumab (also called MLN0002) is approved for the treatment of adult participants with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) who achieved an inadequate response, had a loss of response, or were intolerant to conventional and/or biologic treatments. This study will look at the tolerability and pharmacokinetics of Vedolizumab in participants undergoing allo-HSCT when added to standard GvHD prophylaxis (tacrolimus plus short-term methotrexate) for the prevention of acute GvHD (major complication in allo-HSCT).
The study will enroll approximately 36 participants. Participants will be assigned to different dose-escalating cohorts in order to find out the recommended phase 2 dose (RP2D) of the study:
- Cohort 1: Vedolizumab 75 mg
- Cohort 2: Vedolizumab 300 mg
- Cohort 3: Vedolizumab Dose 1
All participants have to receive 1 injection of Vedolizumab on Day -1 before allo-HSCT and on Days 13 and 42 after allo-HSCT. If none of the participants receiving vedolizumab at 75 mg experience dose-limiting toxicities (DLTs), dose escalation will continue to 300 mg on Day -1 before allo-HSCT and on Days +13 and +42 after allo-HSCT. If the first 3 participants at 300 mg tolerate the treatment without experiencing DLTs, then the decision on whether to increase the vedolizumab IV dose in the next cohort will be guided by the PK results.
Cohorts will be escalated in same manner until the identification of RP2D. The cohort at that dose level may be expanded to include approximately 18 additional participants undergoing myeloablative conditioning or reduced-intensity conditioning (RIC) and receiving either related or unrelated allo-HSCT for the treatment of hematologic malignancies or myeloproliferative neoplasms. This group of participants will allow the further assessment of the tolerability and clinical activity of vedolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is undergoing matched or single-antigen mismatched unrelated-donor myeloablative transplant for the treatment of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML); Is less than or equal to (<=) 60 years of age.
- •For the cohort after RP2D
- •Is undergoing matched or single-antigen mismatched related or unrelated-donor transplant and receiving myeloablative conditioning or RIC for the treatment of hematologic malignancies or myeloproliferative neoplasms; Is less than or equal to (<=) 75 years of age.
排除标准
- •Has received prior allogeneic transplants or who are planned to undergo umbilical cord blood transplant, receive ex vivo T-cell-depleted hematopoietic stem cells (HSCs), received any in vivo T-cell depleting antibodies, or non-myeloablative conditioning.
- •Has active cerebral/meningeal disease, active cytomegalovirus (CMV) colitis, or signs and symptoms of progressive multifocal leukoencephalopathy (PML) or any history of PML.
- •Is undergoing transplant for the treatment of nonmalignant hematological disorders (for example: aplastic anemia, sickle cell anemia, thalassemias, Fanconi anemia).
研究组 & 干预措施
Cohort 1: Vedolizumab 75 mg
Vedolizumab 75 mg, injection, intravenously once on Days -1, 13 and 42.
干预措施: Vedolizumab (Drug)
Cohort 2: Vedolizumab 300 mg
Vedolizumab 300 mg, injection, intravenously once on Days -1, 13 and 42.
干预措施: Vedolizumab (Drug)
Cohort 3: Vedolizumab Dose 1
Vedolizumab first decided dose as determined from Cohort 1 or 2, injection, intravenously once on Days -1, 13 and 42.
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: Baseline up to Day 28
DLTs was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of following events: Grade 3 or higher toxicity assessed by the investigator as related to vedolizumab treatment; Grade 4 or higher regimen-related organ toxicities; and failure to engraft by Day +28. Engraftment was defined as absolute neutrophils count (ANC) greater than (\>) 500 per cubic millimeter (/mm\^3) for 3 consecutive days or \>2000/mm\^3 for 1 day.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Up to 18 weeks after last dose of study drug
Mean Serum Concentrations of Vedolizumab That Helped the Likelihood of Alpha4Beta7 Target Saturation on Day 100 Following Allo-HSCT
时间窗: Day 100
次要结局
- Time to Neutrophil Engraftment(Baseline up to Day 100)
- Percentage of Participants With Overall Grade 2 to 4 Acute Graft-Versus-Host Disease (GvHD)(Baseline up to Day 100)
- Percentage of Participants With Maximum Severity of Acute GvHD Based on Modified Glucksberg Criteria(Baseline up to Day 100)
- Percentage of Participants With Maximum Severity of Acute GvHD Based on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Modified International Bone Marrow Transplant Registry Database (IBMTR) Index(Baseline up to Day 100)
- Ctrough: Serum Concentration Before Dosing for Vedolizumab(Days 13 and 42 pre-dose)