Phase 2 Study of Ruxolitinib-Based Primary Treatment for Acute GVHD
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 98
- 试验地点
- 14
- 主要终点
- Day 28 Treatment Response
研究概览
简要总结
This clinical trial will study ruxolitinib-based treatment of acute graft-versus-host-disease (GVHD) that developed following allogeneic hematopoietic cell transplant. Acute GVHD occurs when donor cells attack the healthy tissue of the body. The most common symptoms are skin rash, jaundice, nausea, vomiting, and/or diarrhea. The standard treatment for GVHD is high dose steroids such as prednisone or methylprednisolone, which suppresses the donor cells, but sometimes there can be either no response or the response does not last. In these cases, the GVHD can become dangerous or even life threatening. High dose steroid treatment can also cause serious complications. Researchers have developed a system, called the Minnesota risk system, to help predict how well the GVHD will respond to steroids based on the symptoms present at the time of diagnosis. The Minnesota risk system classifies patients with newly diagnosed acute GVHD into two groups with highly different responses to standard steroid treatment and long-term outcomes. This protocol maximizes efficiency because all patients with grade II-IV GVHD are eligible for screening and treatment is assigned according to patient risk. Patients with lower risk GVHD, Minnesota standard risk, have high response rates to steroid treatment. In this trial the researchers will test whether ruxolitinib alone is as effective (non-inferior) as steroid-free therapy and safe. Patients will be randomized to two different doses of ruxolitinib to identify the dose which maximizes efficacy while minimizing toxicities such as hematologic and infectious toxicities. Patients with higher risk GVHD, Minnesota high risk, have unacceptable outcomes with systemic corticosteroid treatment alone and the researchers will test whether adding ruxolitinib, a proven effective second line GVHD treatment, can improve outcomes when added to systemic corticosteroids as first line treatment.
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
- None
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
- •Standard risk cohort: Minnesota standard risk GVHD (except patients with grade I [<50% BSA rash])
- •High risk cohort: Minnesota high risk GVHD 3 GVHD that developed after DLI for mixed chimerism or poor graft function is allowed
- •No prior systemic acute GVHD treatment. Topical or non-absorbed steroids are permitted.
- •All donor types, HLA-matches, conditioning regimens, or GVHD prophylaxis strategies are acceptable
- •≥18 years of age
- •Standard risk cohort: Hematopoietic engraftment with absolute neutrophil count (ANC) ≥ 1000/μL and platelet count ≥20,
- •Use of growth factor supplementation and transfusions to maintain adequate hematologic parameters are allowed.
- •High risk cohort: Hematopoietic engraftment with ANC ≥ 500/uL and platelet count ≥20,
- •Use of growth factor supplementation and transfusions to maintain adequate hematologic parameters are allowed.
排除标准
- •Systemic treatment with ruxolitinib or any other JAK inhibitor within 7 days of study entry
- •Prior use of ruxolitinib to treat GVHD at any time
- •Relapsed, progressing or persistent malignancy requiring withdrawal of systemic immunosuppression
- •Relapse prior to development of GVHD unless subsequently in remission for at least 3 months
- •GVHD that developed after DLI for relapse is not allowed without study PI or medical monitor approval
- •Uncontrolled infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
- •Severe organ dysfunction within 3 days of enrollment including requirement for dialysis, mechanical ventilation, continuous BiPAP, or continuous high flow oxygen by nasal cannula, or total bilirubin ≥ 3x upper limit of normal not due to GVHD.
- •A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment (except for mild oral or ocular GVHD)
- •Corticosteroids >10 mg/day methylprednisolone (or other methylprednisolone equivalent, MPE) for any indication within 5 days before the onset of acute GVHD except for adrenal insufficiency or premedication for transfusions/IV meds
- •Participation in clinical trials using experimental agents not approved by the FDA for any indication within 14 days of enrollment or five half-lives, whichever is longer provided any prior adverse events have improved to ≤grade 1
- •Patients who are pregnant or nursing
- •History of allergic reaction to ruxolitinib or any JAK inhibitor
研究组 & 干预措施
Minnesota Standard Risk lower dose
Patients receive lower dose ruxolitinib orally (PO) twice daily (BID) for 56 days then begin taper PO once daily (QD) for 1 week in the absence of disease progression or unacceptable toxicity
干预措施: Ruxolitinib (Drug)
Minnesota Standard Risk higher dose
Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity.
干预措施: Ruxolitinib (Drug)
Minnesota High Risk
Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity. Patients also receive systemic corticosteroid (methylprednisolone or similar) for a minimum of 3 days, then taper dose every 3-5 days in the absence of disease progression or unacceptable toxicity.
干预措施: Ruxolitinib (Drug)
Minnesota High Risk
Patients receive higher dose ruxolitinib PO BID for 56 days then begin taper PO BID for 1 week, followed by PO QD for 1 week in the absence of disease progression or unacceptable toxicity. Patients also receive systemic corticosteroid (methylprednisolone or similar) for a minimum of 3 days, then taper dose every 3-5 days in the absence of disease progression or unacceptable toxicity.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Day 28 Treatment Response
时间窗: 28 days
Day 28 response to treatment defined as complete (CR), very good partial (VGPR), or partial (PR) response without intervening therapy or death to ruxolitinib monotherapy. CR - All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR, the patient must be in CR on the date of assessment and have had no intervening additional GVHD therapy. VGPR - Stage 0 liver and GI and residual stage 1 skin GVHD. For a response to be scored as VGPR, the patient must be in VGPR on the date of assessment and have had no intervening additional GVHD therapy. PR - An improvement by one or more stages in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR, the patient must be in PR on the date of assessment and have had no intervening additional GVHD therapy.
次要结局
- Durable response at day 56(56 days)
- Chronic GVHD requiring systemic steroid treatment(1 year)
- Steroid-refractory GVHD(28 days)
- Cumulative systemic corticosteroid dose(90 days)
- GVHD flares(90 days)
- Overall survival(1 year)
- Non-relapse mortality(1 year)
- Relapse(1 year)
研究者
John Levine
Professor of Internal Medicine and Pediatrics
Icahn School of Medicine at Mount Sinai