NCT03139604已完成3 期
GRAVITAS-301: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Itacitinib or Placebo in Combination With Corticosteroids for the Treatment of First-Line Acute Graft-Versus-Host Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 439
- 试验地点
- 129
- 主要终点
- Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index
研究概览
简要总结
The purpose of this study is to evaluate itacitinib or placebo in combination with corticosteroids as first-line treatment of participants with Grade II to IV acute graft-versus-host disease (aGVHD).
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
- Double (Participant, Investigator)
盲法说明
Double Blind
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
- •Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
- •Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen.
- •Evidence of myeloid engraftment. Use of growth factor supplementation is allowed.
- •Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min measured or calculated by Cockroft Gault equation.
- •Willing to avoid pregnancy or fathering children.
- •Able to give written informed consent and comply with all study visits and procedures.
- •Able to swallow and retain oral medication.
排除标准
- •Has received more than 1 allo-HSCT.
- •Has received more than 2 days of systemic corticosteroids for aGVHD.
- •Presence of GVHD overlap syndrome.
- •Presence of an active uncontrolled infection.
- •Known human immunodeficiency virus infection.
- •Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation.
- •Participants with evidence of relapsed primary disease, or participants who have been treated for relapse after the allo-HSCT was performed.
- •Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization.
- •Severe organ dysfunction unrelated to underlying GVHD, including:
- •Cholestatic disorders or unresolved veno-occlusive disease of the liver.
- •Clinically significant or uncontrolled cardiac disease.
- •Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
- •Currently breast feeding.
- •Received JAK inhibitor therapy after allo-HSCT for any indication. Treatment with a JAK inhibitor before allo-HSCT is permitted.
- •Treatment with any other investigational agent, device, or procedure within 21 days (or 5 half-lives, whichever is greater) of enrollment.
- •Any medical complications or conditions 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 participant; or interfere with interpretation of study data.
- •Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
研究组 & 干预措施
Itacitinib
Experimental
Itacitinib plus corticosteroids
干预措施: Itacitinib (Drug)
Itacitinib
Experimental
Itacitinib plus corticosteroids
干预措施: Prednisone (Drug)
Itacitinib
Experimental
Itacitinib plus corticosteroids
干预措施: Methylprednisolone (Drug)
Placebo
Placebo Comparator
Matching placebo plus corticosteroids
干预措施: Placebo (Drug)
Placebo
Placebo Comparator
Matching placebo plus corticosteroids
干预措施: Prednisone (Drug)
Placebo
Placebo Comparator
Matching placebo plus corticosteroids
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Overall Response Rate Based on Center for International Blood and Marrow Transplant Research (CIBMTR) Response Index
时间窗: Day 28
Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
次要结局
- Nonrelapse Mortality(Month 6,9,12 and 24)
- Duration of Response(Baseline through 30-35 days after end of treatment, total particpation expected to average 24 months)
- Cmax of Itacitinib When Administered in Combination With Corticosteroids(Protocol-defined timepoints up to Day 28)
- Cmin of Itacitinib When Administered in Combination With Corticosteroids(Protocol-defined timepoints up to Day 28)
- Tmax of Itacitinib When Administered in Combination With Corticosteroids(Protocol-defined timepoints up to Day 28)
- AUC of Itacitinib When Administered in Combination With Corticosteroids(Protocol-defined timepoints up to Day 28)
- CL/F of Itacitinib When Administered in Combination With Corticosteroids(Protocol-defined timepoints up to Day 28)
- Time to Response(End of Study, total particpation expected to average 24 months)
- Relapse Rate of Malignant and Nonmalignant Hematologic Disease(Randomization through end of Study, study duration expected to average 24 months)
- Malignancy Relapse-related Mortality Rate(Randomization through end of Study, study duration expected to average 24 months)
- Failure-free Survival(6 months from randomization)
- Overall Survival (OS)(End of Study up to approximately 24 months)
- Number of Treatment-emergent Adverse Events With INCB39110(30-35 days after end of treatment, approximately 24 months)
- Incidence Rate of Secondary Graft Failure(Randomization through end of Study, study duration expected to average 24 months)
- Proportion of Subjects Who Discontinue Corticosteroids(Days 28, 56, 100, and 180)
- Proportion of Subjects Who Discontinue Immunosuppressive Medications(Days 56 and 100)
- Incidence Rate of aGVHD Flares(up to day 100)
- Incidence Rate of cGVHD(Days 180 and 365)
- Objective Response Rate(Days 14, 56 and 100)
研究者
研究点 (129)
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