Phase II Trial Evaluating the Safety and Efficacy of Atorvastatin for the Prophylaxis of Acute Graft Versus Host Disease(GVHD) in Patients With Hematological Malignancies Undergoing HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation (HSCT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Grades II to IV aGVHD at Day +100 of Atorvastatin Administration
研究概览
简要总结
Phase II trial evaluating the safety & efficacy of Atorvastatin for prophylaxis of Acute Graft Versus Host Disease (GVHD) in patients with hematological malignances undergoing human leukocyte antigen (HLA)-Matched Related Donor Hematopoietic Stem Cell Transplant (HSCT).
详细描述
The study is a single-arm phase II single institutional trial evaluating the safety and efficacy of atorvastatin for the prophylaxis of acute GVHD in patients with hematological malignancies undergoing HLA matched related donor HSCT. This study will explore a two-pronged acute GVHD prophylaxis strategy, consisting of pre-treating consenting related donors with atorvastatin before stem cell mobilization and collection, followed by atorvastatin plus methotrexate/tacrolimus-based GVHD prophylaxis in transplant recipient patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Donor Eligibility Criteria
- •The donor must be at least 18 years of age, and willing/able to provide informed consent. Complete medication list will be reviewed for potential negative interaction with atorvastatin.
- •The donor must be an HLA-matched sibling or relative.
- •Syngeneic donors are not eligible.
- •Female donors of child-bearing potential should have a negative pregnancy test, and must not be breast feeding.
- •Bilirubin, AST and ALT must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
- •Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
- •Adequate cardiac function with no history of congestive heart failure, uncontrolled atrial fibrillation or ventricular tachyarrhythmias.
- •Patient Eligibility Criteria
- •Have hematologic malignancy requiring allogeneic HSCT, have adequate organ function, a serologic (or higher resolution) 6/6 class I human leukocyte antigen (HLA)-A and B and molecular class II DRB1 matched related donor, and are able to give informed consent.
- •Patients > 18 and ≤ 65 years with comorbidity score ≤ 3 will be eligible for myeloablative conditioning (MAC), while patients > 65 years of age, those with previous history of autologous transplantation, or high comorbidity index (>3) will be eligible for reduced intensity conditioning (RIC) transplantation .
- •All patients must have at least one 6/6 HLA-matched sibling donor.
- •Patient must provide informed consent
- •Patients must have left ventricular ejection fraction > 30%, no uncontrolled arrhythmias or New York Heart Association class III-IV heart failure.
- •Bilirubin must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be <2 x normal; and absence of hepatic fibrosis/cirrhosis.
- •Serum creatinine clearance of ≥40% of normal calculated by Cockcroft-Gault equation.
- •Forced expiratory volume in one second (FEV1)and diffusion capacity; corrected for hemoglobin(DLCO) ≥ 50% and 40% of predicted respectively.
- •Karnofsky performance status >
- •A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
- •No HIV infection. Patients with immune dysfunction are at a significantly higher risk of toxicities from intensive immunosuppressive therapies.
- •No evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
- •No active alcohol or substance abuse within 6 months of study entry.
- •Prior allogeneic transplant is acceptable.
- •No history of intolerance or allergic reactions with atorvastatin or other statins.
- •Patients who have previously been taking atorvastatin or any other statin will be eligible as long as there is no contraindication to switch to atorvastatin 40mg/day in the opinion of the treating physician.
排除标准
- •Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.
- •Patients receiving another investigational drug are not eligible unless cleared by Principal Investigator. Patients with prior malignancies except resected basal cell carcinoma, treated carcinoma in-situ, or other hematologic diseases for which allogeneic HSCT is a treatment strategy, are not eligible. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Principal Investigator.
研究组 & 干预措施
Donor
Related donors will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines. Peripheral blood stem cells will not be manipulated or T-depleted prior to administration.
干预措施: atorvastatin (Drug)
Patient
Patients will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first. Standard post transplant care will be administered.
干预措施: atorvastatin (Drug)
Patient
Patients will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first. Standard post transplant care will be administered.
干预措施: Tacrolimus (Drug)
Patient
Patients will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first. Standard post transplant care will be administered.
干预措施: methotrexate (Drug)
结局指标
主要结局
Percentage of Participants With Grades II to IV aGVHD at Day +100 of Atorvastatin Administration
时间窗: Up through day 100 following transplant
The incidence of grades II to IV aGVHD at day +100 of atorvastatin administration. The grading of aGVHD and cGVHD were done using the Consensus Conference criteria.
次要结局
- Safety of Atorvastatin in Transplant Recipients in Terms of Adverse Events and Toxicities.(Patients: Baseline, weekly for 9 weeks and then on days 84, 91-100, 180 and 365. Donors: at apheresis and then 30 days later.)
- Time to Neutrophil and Platelet Engraftment(weekly for 12 weeks, 100 days, 6 months, and 12 months)
- Percentage of Patients With Chronic Graft Versus Host Disease (cGVHD)(up 1 year post transplant)
- Non Relapse Mortality (NRM) at One Year(up to 12 months post transplant)
研究者
Yvonne Efebera
Principal Investigator
Ohio State University Comprehensive Cancer Center