NCT03774082已完成2 期
A Phase II Open-label, Single-arm, Multi-center Study of Ruxolitinib Added to Corticosteroids in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplantation
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) at Cycle 7 Day 1
研究概览
简要总结
This open-label, single-arm, Phase II multi-center study enrolled 46 participants and investigated the activity, pharmacokinetics and safety of ruxolitinib added to the subject's immunosuppressive regimen among infants, children, and adolescents aged ≥28 days to <18 years old with either moderate to severe treatment-naive cGvHD or SR-cGvHD.
Although 46 participants were enrolled,1 participant (enrolled in the ≥6y to <12y age group) received study treatment beyond protocol requirements and was excluded from analyses.
详细描述
Subjects were grouped according to their age as follows:
- Group 1 included subjects ≥12y to <18y
- Group 2 included subjects ≥6y to <12y
- Group 3 included subjects ≥2y to <6y and
- Group 4 included subjects ≥28days to <2y. Enrollment initiation into the youngest age group, Group 4, was subject to the availability of data in this age group from another study, as well as a review of available PK, safety, and activity data generated from Groups 1 to 3 in the current study. At least 5 evaluable participants per group were needed for the primary analysis in Groups 1, 2 and 3. No minimum number of evaluable participants were needed in Group 4. Enrollment was completed prior to the availability of the data and so no subjects were enrolled in Group 4.
After a screening period of Day -28 to Day -1: eligible subjects started study treatment on Cycle
1 Day 1 and were treated for up to a maximum of 3 years (39 cycles/156 weeks) or until early discontinuation. Subjects who discontinued study treatment for any reason earlier than 39 cycles were followed every 6 months until 3 years from their first dose of study treatment was reached.
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
- 28 Days 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects age ≥28 days and <18 years at the time of informed consent.
- •Subjects who have undergone a successful alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of myeloablative or reduced intensity conditioning are eligible.
- •Subjects with diagnosed moderate to severe cGvHD according to NIH 2014 Consensus Criteria prior to Cycle 1 Day
- •Other possible diagnoses for clinical symptoms supporting cGvHD diagnoses must be excluded (e.g., infection, drug side effects, malignancy). Subjects must be either:
- •Treatment-naive cGvHD subjects that have not received any prior systemic treatment for cGvHD except for a maximum 72h of prior systemic corticosteroid therapy of methylprednisolone or equivalent after the onset of chronic GvHD. Subjects are allowed to have received prior systemic treatment for cGvHD prophylaxis (as long as the prophylaxis was started prior to the diagnosis of cGvHD).
- •OR o Steroid-refractory moderate to severe cGvHD as per institutional criteria, or per physician decision in case institutional criteria are not available, and still receiving systemic corticosteroids for the treatment of cGvHD for a duration of <18 months prior to Cycle 1 Day
- •In case the corticosteroids were previously interrupted due to response, the duration of < 18 months applies to the last period of corticosteroid use.
排除标准
- •SR-cGvHD subjects with a prior cGvHD treatment with a JAK1- or a JAK2- or a JAK1/2-inhibitor, except when the subject achieved complete or partial response and has been off JAK inhibitor treatment for at least 4 weeks prior to Cycle Day 1 or up to 5 times the half-life of the prior JAK inhibitor, whichever is longer.
- •* Subjects who initiated systemic calcineurin inhibitors (CNI; cyclosporine or tacrolimus) within 3 weeks prior to start of ruxolitinib on Cycle 1 Day
- •Note: systemic CNI are allowed when initiated > 3 weeks from start of ruxolitinib.
- •Failed prior alloSCT within the past 6 months
- •Significant respiratory disease including subjects who are on mechanical ventilation or who have a resting oxygen saturation < 90% by pulse-oximetry on room-air.
- •Impairment of gastrointestinal (GI) function (unrelated to GvHD) or GI disease (unrelated to GvHD) that may significantly alter the absorption of oral ruxolitinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection),
- •Cholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to cGvHD and ongoing organ dysfunction)
- •Presence of clinically active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
- •Known human immunodeficiency virus (HIV) infection.
- •Evidence of uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV) based on assessment done by Investigator or delegate.
- •Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
- •History of bone disorders such as osteogenesis imperfecta, rickets, renal osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc. prior to the underlying diagnosis which resulted in the alloSCT.
- •History of endocrine or kidney related growth retardation prior to the underlying diagnosis which resulted in the alloSCT.
- •Evidence of clinically active tuberculosis (clinical diagnosis per local practice)
- •Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/daymethylprednisolone (or equivalent prednisone dose 1.25 mg/kg/day) within 7 days of the screening visit.
- •History of progressive multifocal leuko-encephalopathy (PML).
- •Presence of severely impaired renal function
研究组 & 干预措施
INC424 (ruxolitinib)
Experimental
All pediatric participants received ruxolitinib twice a day (BID) in either tablet or oral solution (liquid), depending on the group they were in.
干预措施: INC424 (Drug)
结局指标
主要结局
Overall Response Rate (ORR) at Cycle 7 Day 1
时间窗: At Cycle 7 Day 1 (Day 168); Cycle = 28 Days
ORR is defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. The response is assessed per National Institute of Health (NIH) consensus criteria and scoring of response was relative to the organ stage at the start of study treatment.
次要结局
- Ruxolitinib Concentrations by Timepoint(Cycle 1 Day 1: 0.5, 2 and 6 hours post-dose; Pre-dose on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 3 Day 1, Cycle 5 Day 1 and Cycle 7 Day 1; Cycle = 28 Days)
- Duration of Response (DOR)(From baseline up to 39 cycles; Cycle = 28 Days)
- Overall Response Rate (ORR) at Cycle 4 Day 1(At Cycle 4 Day 1 (Day 84); Cycle = 28 Days)
- Best Overall Response (BOR)(Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD; Cycle = 28 Days)
- Failure Free Survival (FFS)(From baseline up to 39 cycles; Cycle = 28 Days)
- Cumulative Incidence of Malignancy Relapse/Recurrence (MR)(From baseline up to 39 cycles; Cycle = 28 Days)
- Non-relapse Mortality (NRM)(From baseline up to 39 cycles; Cycle = 28 Days)
- Overall Survival (OS)(From baseline up to 39 cycles; Cycle = 28 Days)
- Percentage of Participants With ≥50% Reduction From Baseline in Daily Corticosteroid Dose(Baseline to Cycle 7 Day 1 (Day 168); Cycle = 28 Days)
- Percentage of Participants With a Reduction to a Low Dose Corticosteriod(Baseline to Cycle 7 Day 1 (Day 168); Cycle = 28 Days)
- Graft Failure(From baseline up to 39 cycles; Cycle = 28 Days)
研究者
研究点 (1)
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