Graft-versus-host Disease Prophylaxis With Post-transplantation Cyclophosphamide and Ruxolitinib in Patients With Myelofibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of chronic GVHD, moderate and severe (NIH criteria)
研究概览
简要总结
A number of groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical and unrelated allogeneic stem cell transplantation (SCT). Still the relapse of the underlining malignancy is a problem after this prophylaxis. Ruxolitinib is currently one of the most promising drugs in the treatment of steroid-refractory GVHD. On the other hand, its primary indication is myelofibrosis, and it was demonstrated that ruxolitinib before allogeneic SCT might improve the outcome. This pilot trial evaluates whether the combination of PTCy and ruxolitinib facilitates adequate GVHD control, and decreases the risk of graft failure and disease progression in myelofibrosis patients.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have an indication for allogeneic hematopoietic stem cell transplantation
- •Diagnosis:
- •Primary myelofibrosis Secondary myelofibrosis
- •Signed informed consent
- •Matched related, 8-10/10 HLA-matched unrelated or haploidentical donor available. The HLA typing is performed by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB
- •No second tumors
- •No severe concurrent illness
排除标准
- •Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
- •Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
- •Respiratory distress >grade I
- •Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >2 upper normal limits
- •Creatinine clearance < 60 mL/min
- •Uncontrolled bacterial or fungal infection at the time of enrollment
- •Requirement for vasopressor support at the time of enrollment
- •Karnofsky index <30%
- •Pregnancy
- •Somatic or psychiatric disorder making the patient unable to sign informed consent
研究组 & 干预措施
PTCy and ruxolitinib
干预措施: Allogeneic hematopoietic stem cell transplantation (Procedure)
PTCy and ruxolitinib
干预措施: Busulfan (Drug)
PTCy and ruxolitinib
干预措施: Fludarabine monophosphate (Drug)
PTCy and ruxolitinib
干预措施: Cyclophosphamide (Drug)
PTCy and ruxolitinib
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Incidence of chronic GVHD, moderate and severe (NIH criteria)
时间窗: 365 days
Incidence of acute graft-versus-host disease, grades II-IV
时间窗: 180 days
次要结局
- Incidence of primary or secondary graft failure(60 days)
- Event-free survival analysis(365 days)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03(100 days)
- Non-relapse mortality analysis(365 days)
- Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence(100 days)
- Overall survival analysis(365 days)
- Relapse rate analysis(365 days)
研究者
Ivan S Moiseev
Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation
St. Petersburg State Pavlov Medical University