GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 155
- 试验地点
- 133
- 主要终点
- Part 1: 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 efficacy and safety of itacitinib in combination with corticosteroids as first-line treatment for moderate or severe chronic graft-versus-host disease (cGVHD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Active, clinically diagnosed, moderate or severe cGVHD per NIH Consensus Criteria
- •Underwent allogeneic stem cell transplantation (allo-HCT)
- •Karnofsky Performance Status score ≥ 60%.
- •Evidence of myeloid and platelet engraftment.
- •Willingness to avoid pregnancy or fathering children based on protocol-defined criteria.
排除标准
- •Has received more than 3 days/72 hours of systemic corticosteroid treatment for cGVHD.
- •Has received any other systemic treatment for cGVHD, including extracorporeal photopheresis (ECP).
- •Prior treatment with a Janus kinase (JAK) inhibitor for acute GVHD, unless the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks before randomization.
- •cGVHD occurring after a nonscheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence.
- •Evidence of relapsed primary malignancy.
研究组 & 干预措施
Part 1 : Dose determination of itacitinib
itacitinib administered in combination with corticosteroids.
干预措施: Itacitinib (Drug)
Part 1 : Dose determination of itacitinib
itacitinib administered in combination with corticosteroids.
干预措施: Methylprednisolone (Drug)
Part 1 : Dose determination of itacitinib
itacitinib administered in combination with corticosteroids.
干预措施: Prednisone (Drug)
Part 1 : Dose expansion of itacitinib
itacitinib administered in combination with corticosteroids or corticosteroids alone.
干预措施: Itacitinib (Drug)
Part 1 : Dose expansion of itacitinib
itacitinib administered in combination with corticosteroids or corticosteroids alone.
干预措施: Placebo (Drug)
Part 1 : Dose expansion of itacitinib
itacitinib administered in combination with corticosteroids or corticosteroids alone.
干预措施: Methylprednisolone (Drug)
Part 1 : Dose expansion of itacitinib
itacitinib administered in combination with corticosteroids or corticosteroids alone.
干预措施: Prednisone (Drug)
Part 2 : itacitinib recommended dose from part 1
itacitinib or placebo administered in combination with corticosteroids
干预措施: Itacitinib (Drug)
Part 2 : itacitinib recommended dose from part 1
itacitinib or placebo administered in combination with corticosteroids
干预措施: Methylprednisolone (Drug)
Part 2 : itacitinib recommended dose from part 1
itacitinib or placebo administered in combination with corticosteroids
干预措施: Prednisone (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: up to Day 28
A DLT was defined as the occurrence of any protocol-defined toxicity with onset up to and including Day 28, except those with a clear alternative explanation. Participants who received at least 21 of 28 doses of study drug at the level assigned or had a DLT were considered evaluable for determining tolerability of the dose. Participants who did not achieve this duration of exposure and did not have a DLT were to be replaced for purposes of toxicity identification.
Part 1 Expansion: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
时间窗: until at least 30 days after the last dose of study treatment (up to 1103 days)
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Part 2: Response Rate at Month 6
时间窗: Month 6
Response rate was defined as the percentage of participants that had complete response (CR) or partial response (PR), per National Institutes of Health (NIH) Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
次要结局
- Part 1 Expansion: Response Rate at Months 3 and 6(Months 3 and 6)
- Parts 1 and 1 Expansion: Cmax of Itacitinib(Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose)
- Parts 1 and 1 Expansion: Ctau of Itacitinib(Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing))
- Parts 1 and 1 Expansion: Tmax of Itacitinib(Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing))
- Parts 1 and 1 Expansion: Cl/F of Itacitinib(Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing))
- Part 2: Cmax of Itacitinib(Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose)
- Part 2: Cmin of Itacitinib(Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose)
- Part 2: Tmax of Itacitinib(Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose)
- Part 2: AUC0-t of Itacitinib(Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose)
- Part 2: Cl/F of Itacitinib(Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose)
- Part 1: Response Rate at Months 3, 6, and 12(Months 3, 6, and 12)
- Part 1 Expansion: Response Rate at Month 12(Month 12)
- Part 1 Expansion: Time to Response(up to Month 12)
- Part 1 Expansion: Duration of Response(up to 24 months)
- Part 1 Expansion: Overall Survival(up to 36 months)
- Part 1 Expansion: Nonrelapse Mortality (NRM) Rate(up to 24 months)
- Part 1 Expansion: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1(Day 1; Day 180)
- Part 1 Expansion: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180(Day 180)
- Part 2: Percentage of Participants Successfully Tapered Off All Corticosteroids at Day 180(Day 180)
- Part 1 Expansion: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases(up to 1073 days)
- Part 1 Expansion: Time to Primary Hematologic Disease Relapse(up to 24 months)
- Part 2: Change From Baseline in Lee cGVHD Symptom Scale (LLS) Scores(Baseline; End of Treatment in Phase 2)
- Part 2: Change From Baseline in Quality of Life-Short Form-36 Version 2 (QOL-SF-36 v2) Scores(Baseline; End of Treatment in Phase 2)
- Part 2: Change From Baseline in Patient Global Impression of Change (PGIC) Responses(Baseline; End of Treatment in Phase 2)
- Part 2: Change From Baseline in EQ-5D-3L Scores(Baseline; End of Treatment in Phase 2)
- Part 2: Change From Baseline in Patient Global Impression of Severity (PGIS) Responses(Baseline; End of Treatment in Phase 2)
- Part 2: Response Rate at Months 3 and 12(Months 3 and 12)
- Part 2: Duration of Response(up to 24 months)
- Part 2: Overall Survival(up to 36 months)
- Part 2: NRM Rate(up to 24 months)
- Part 2: Percentage of Participants With a ≥50% Reduction in Daily Corticosteroid Dose at Day 180 From the Corticosteroid Dose on Day 1(Day 1; Day 180)
- Part 2: Relapse Rate of Malignant and Nonmalignant Hematologic Diseases(up to 24 months)
- Part 2: Time to Primary Hematologic Disease Relapse(up to 24 months)
- Part 2: Number of Participants With Any TEAE(up to 30 days after the last dose in Phase 2)