NCT03339297已完成2 期
A Phase 2, Prospective, Randomized, Open-Label Study on the Efficacy of Defibrotide Added to Standard of Care Immunoprophylaxis for the Prevention of Acute Graft-versus-Host-Disease in Adult and Pediatric Patients After Allogeneic Hematopoietic Stem Cell Transplant
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
- 152
- 试验地点
- 62
- 主要终点
- Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT)
研究概览
简要总结
This is a study comparing the defibrotide prophylaxis arm vs standard of care arm for the prevention of aGvHD.
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
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥1 year of age at screening and undergoing allogeneic Hematopoietic Stem Cell Transplant (HSCT).
- •Participant must be diagnosed with acute leukemia in morphologic complete remission (CR1 or CR2) or with Myelodysplastic syndrome (MDS) with no circulating blasts and with less than 5% blasts in the bone marrow
- •Participant must have planned to receive either a myeloablative or reduced-intensity conditioning regimen and have an unrelated donor who is human leukocyte antigen (HLA) matched or single-allele mismatched
- •Participant must receive the following medical regimen as part of standard of care immunoprophylaxis for GvHD in either study arm at doses and regimen determined by local institutional guidelines, physician preference, and participant need:
- •Methotrexate (MTX) or Mycophenolate mofetil (MMF) + calcineurin inhibitor (Cyclosporine A [CSA] or Tacrolimus [TAC]) +/- Anti-thymocyte globulin (ATG) (ATG use is limited to 30% of participants).
- •Graft must be a CD3+ T-cell replete peripheral blood stem cell (PBSC) graft or non-manipulated bone marrow (BM) graft.
- •Adult participants must be able to understand and sign a written informed consent. For pediatric participants, the parent/legal guardian or representative must be able to understand and sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
排除标准
- •Participant has had a prior autologous or allogeneic HSCT.
- •Participant is using or plans to use an investigational agent for the prevention of GvHD.
- •Participant is receiving or plans to receive other investigational therapy and/or is enrolled or plans to enroll in a separate clinical study.
- •Participant, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- •Participant has a psychiatric illness that would prevent the participant or legal guardian or representative from giving informed consent and/or assent.
- •Participant has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study.
- •Participant is pregnant or lactating and does not agree to stop breastfeeding.
- •Any other condition that would cause a risk to the participant if he/she participated in the trial.
- •Participant has a known history of hypersensitivity to defibrotide or any of the excipients.
- •Participant had acute bleeding that is clinically significant within 24 hours before the start of study treatment, defined as either of the following:
- •Hemorrhage requiring >15 cc/kg of packed red blood cells (eg, pediatric participant weighing 20 kg and requiring 300 cc packed red blood cells/24 hours, or an adult weighing >70 kg and requiring 3 units of packed red blood cells/24hours) to replace blood loss, or
- •Bleeding from a site which, in the investigator's opinion, constituted a potential life-threatening source (eg, pulmonary hemorrhage or central nervous system bleeding), irrespective of amount of blood loss
- •Participant used any medication that increases the risk of bleeding within 24 hours before the start of study treatment, including, but not limited to, systemic heparin, low molecular weight heparin, heparin analogs, alteplase, streptokinase, urokinase, antithrombin III, oral anticoagulants including warfarin, and other agents that increase the risk of bleeding. Participants may have received heparin or other anticoagulants for routine central venous line management and intermittent dialysis or ultrafiltration. Fibrinolytic instillation for central venous line occlusion was also permitted. Note: Heparin used to keep catheters open was allowed (up to 100 U/kg/day).
研究组 & 干预措施
Defibrotide Prophylaxis
Experimental
Standard of Care Immunoprophylaxis + Defibrotide
干预措施: Defibrotide (Drug)
Defibrotide Prophylaxis
Experimental
Standard of Care Immunoprophylaxis + Defibrotide
干预措施: Standard of Care (Drug)
Standard of Care
Active Comparator
Standard of Care Immunoprophylaxis Alone
干预措施: Standard of Care (Drug)
结局指标
主要结局
Cumulative Incidence Percentage of Grade B to D Acute Graft Versus Host Disease (aGvHD) by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT)
时间窗: HSCT Day (Day +0 post-HSCT) through Day +100 post-HSCT
Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the International Bone Marrow Transplant Registry (IBMTR) Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
次要结局
- Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years(Baseline through Day +100 post-HSCT)
- Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Mobility Dimension for Participants With Age >=16 Years(Baseline through Day +180 post-HSCT)
- Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years(Baseline through Day +100 post-HSCT)
- Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Pain/Discomfort Dimension for Participants With Age >=16 Years(Baseline through Day +180 post-HSCT)
- Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years(Baseline through Day +100 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes as Measured Based on the EQ Visual Analog Scale (EQ VAS)(Baseline through Days +100 and +180 post-HSCT)
- Cumulative Incidence Percentage of Grade B to D aGvHD by Day +180 Post-HSCT(HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT)
- Cumulative Incidence Percentage of Systemic Steroids for the Treatment of aGvHD +180 Days Post-HSCT(HSCT Day (Day +0 post-HSCT) through Day +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the Physical Wellbeing Subscale as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score(Baseline through Days +100 and +180 post HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the General (FACT-G) Questionnaire Score(Baseline through Days +100 and +180 post-HSCT)
- Kaplan-Meier Estimate of Grade B to D aGvHD-free Survival by Days +100 and +180 Post-HSCT(HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT)
- Cumulative Incidence Percentage of Grade C to D aGvHD by Days +100 and +180 Post-HSCT(HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT)
- Cumulative Incidence Percentage of Disease Relapse by Days +100 and +180 Post-HSCT(HSCT Day (Day +0 post-HSCT) through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the Social/Family Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the Emotional Wellbeing Subscale as Measured by the FACT-BMT Questionnaire Score(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the Bone Marrow Transplantation Subscale (BMTS) as Measured by the FACT-BMT Questionnaire Score(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the FACT-BMT Total Score(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant-Trial Outcomes Index (FACT-BMT-TOI)(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Days +100 and +180 Post-HSCT in Participant Reported Outcomes Measured Based on the EQ-5D-5L Index Value for Health States(Baseline through Days +100 and +180 post-HSCT)
- Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Self-Care Dimension for Participants With Age >=16 Years(Baseline through Day +180 post-HSCT)
- Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years(Baseline through Day +100 post-HSCT)
- Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Usual Activities Dimension for Participants With Age >=16 Years(Baseline through Day +180 post-HSCT)
- Change From Baseline to Day +100 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years(Baseline through Day +100 post-HSCT)
- Change From Baseline to Day +180 Post-HSCT in 5-Level European Quality of Life (EQ-5D-5L) Anxiety/Depression Dimension for Participants With Age >=16 Years(Baseline through Day +180 post-HSCT)
研究者
研究点 (62)
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