A Phase II Trial of De-escalated PTCy and Ruxolitinib for GVHD Prophylaxis in Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- The number of subjects who experience GVHD-free survival.
研究概览
简要总结
This is an open-label phase 2 study designed to explore the efficacy and safety of low-dose PTCy-ruxolitinib GVHD prophylaxis in older adults undergoing allogeneic HCT with a matched sibling or unrelated donor with a peripheral blood stem cell graft.
详细描述
Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of hematologic malignancy.
- •Must be in remission:
- •Acute Leukemia, chronic leukemia, or myelodysplasia/myeloproliferative neoplasm (excluding primary myelofibrosis): No circulating blasts and <5% blasts in the bone marrow.
- •Hodgkin and non-Hodgkin lymphomas: Chemo-sensitive disease at time of transplant
- •Patients must have a related or unrelated peripheral blood stem cell donor that is an 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing. Unrelated donors must be willing to donate peripheral blood stem cells and meet NMDP criteria for donation.
- •Planned reduced intensity conditioning therapy with fludarabine/melphalan, with total dose of melphalan of 100-140 mg/m^2 IV or fludarabine/busulfan with total dose of busulfan of 6.4 mg/kg IV.
- •Karnofsky Performance Scale of 60 or greater.
- •Male participants must agree to abstinence or to use of barrier contraception during the entire study period.
- •Female participants of childbearing potential will require a negative pregnancy test and should agree to practice two effective methods of contraception during the entire study period.
- •Ability to understand a written informed consent document, and the willingness to sign it.
排除标准
- •Prior allogeneic HCT or Chimeric antigen receptor (CAR) -T cell therapy.
- •Patients with liver dysfunction evidenced by bilirubin ≥2x upper limit normal (ULN), except for a history of Gilbert syndrome.
- •Patients with renal impairment defined by creatinine<2mg/dL.
- •Patients with cardiac dysfunction defined by a left ventricular ejection fraction ≤45%.
- •Patients with pulmonary dysfunction defined by a forced expiratory volume in the first second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) ≤50% of predicted.
- •Patients with a chronic or active infection requiring systemic treatment during and after transplant.
- •Presence of other active malignant disease diagnosed within 12 months, except for adequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 or less, or cervical intraepithelial neoplasia. Active malignancy is malignancy receiving treatment.
- •Pregnant or lactating subjects.
研究组 & 干预措施
Graft-versus-host disease prophylaxis
Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.
干预措施: Cyclophosphamide (Drug)
Graft-versus-host disease prophylaxis
Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.
干预措施: Tacrolimus (Drug)
Graft-versus-host disease prophylaxis
Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.
干预措施: Mycophenolate Mofetil (Drug)
Graft-versus-host disease prophylaxis
Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 5 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
The number of subjects who experience GVHD-free survival.
时间窗: One year (365 Days) after hematopoietic cell transplantation (HCT)
This measure is defined as being alive without having experienced grade III/IV acute GVHD, or chronic GVHD requiring systemic immune suppression.
次要结局
- Overall survival at one year.(One year after HCT)
- The number of subjects with chronic GVHD at one year.(One year after HCT)
- The number of subjects with non-relapse mortality at one year.(One year after HCT)
- The number of subjects with acute GVHD at Day +100.(Day +100 after HCT)
- The number of subjects with acute GVHD at Day +180.(Day +180 after HCT)
- The number of subjects with non-relapse mortality at Day +100.(Day +100 after HCT)
研究者
Sameem M. Abedin, MD
Associate Professor
Medical College of Wisconsin