Safety and Efficacy of Maraviroc-Based Graft-Versus-Host-Disease Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Donor Transplantation
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Incidence of Acute GVHD Grades II-IV
研究概览
简要总结
HLA-mismatched unrelated donor (MMUD) and HLA-haploidentical donor (Haplo Donor) hematopoietic stem cell transplantation (HSCT) is associated with increased graft-versus-host-disease (GVHD) and impaired survival. The chemokine receptor 5 (CCR5) antagonist maraviroc has immunomodulatory properties potentially beneficial for GVHD control as it can blockade lymphocyte chemotaxis without impairing T-cell function. The aim of this study is to evaluate the safety and efficacy of maraviroc combined with standard graft-versus-host-disease prophylaxis in patients with hematologic malignancies after allogeneic stem cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors. Based on the results of our previously small sample study with maraviroc combined with cyclosporine/tacrolimus and methotrexate for prophylaxis of GVHD, the investigators plan to perform the clinical trail.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 12-65 years (patient is older than 12.0 and less than 66.0 years old)
- •Patients with acute leukemia, myelodysplastic syndrome or lymphoma who scheduled to undergo allogeneic stem-cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors
- •Renal function: estimated creatinine clearance greater than 40 mL/minute (using the Cockcroft-Gault formula and actual body weight)
- •Hepatic function: Baseline direct bilirubin, alanine aminotransferase (ALT) lower than three times the upper limit of normal
- •Pulmonary disease: forced vital capacity (FVC) or forced expiratory volume at one second (FEV1) > 40% predicted
- •Cardiac ejection fraction > 40%
- •Signed informed consent
排除标准
- •Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
- •Prior allogeneic transplant
- •Karnofsky Performance Score < 70%
- •Patients who are not undergoing standard GVHD prophylaxis with cyclosporine/tacrolimus and methotrexate
- •Patients with uncontrolled bacterial, viral or fungal infections
- •Patients receiving other investigational drugs for GVHD
研究组 & 干预措施
Maraviroc + standard GVHD prophylaxis
Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
干预措施: Maraviroc (Drug)
Maraviroc + standard GVHD prophylaxis
Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
干预措施: Cyclosporine (in HLA-Unrelated Donor Transplantation) (Drug)
Maraviroc + standard GVHD prophylaxis
Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
干预措施: Tacrolimus (in HLA-Mismatched Related Donor Transplantation) (Drug)
Maraviroc + standard GVHD prophylaxis
Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Incidence of Acute GVHD Grades II-IV
时间窗: 1 Year
次要结局
- Overall Survival(1 Year)
- Incidence of Acute GVHD Grades III-IV(By day +100 post-HSCT)
- Incidence of Transplant-Related Mortality(By day +100 post-HSCT)
- Frequency of Grade 3 or Greater Toxicities(Up to day +100 post-HSCT)
- Disease Relapse or Progression(1 Year)
- Incidence of Chronic GVHD(1 Year)
- Hematologic Recovery (Neutrophils and Platelets)(Up to day +100 post-HSCT)
- Incidence of Grade 2 and 3 Infections(1 Year)