A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
研究概览
简要总结
The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".
详细描述
The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1.
The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •One of the following diagnoses with histological confirmation by the Pathology Department at H. Lee Moffitt Cancer Center:
- •Acute Lymphocytic Leukemia (ALL) in complete remission 1 (CR1) with t(9:22) or t(4:11), or any ALL beyond CR1
- •Acute Myelogenous Leukemia (AML) with high risk cytogenetics in CR1 as defined by Bloomfield any AML beyond CR1
- •Myelodysplastic Syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1
- •Chronic myelomonocytic leukemia (CMML)
- •Chronic Myelogenous Leukemia (CML) with Imatinib-refractory chronic phase, or beyond chronic phase by morphology or cytogenetics
- •Myelofibrosis
- •Severe aplastic anemia
- •Chemosensitive Non-Hodgkin's lymphoma and Hodgkin's disease that are not candidate to autologous transplant due to prior autologous transplantation
- •Multiple Myeloma patient not candidate for autologous stem cell transplantation
- •Karnofsky performance status ≥ 70% (adult)
- •Normal organ and marrow function as defined below:
- •Hepatic: Total bilirubin must be less than or equal to 2mg/dL (Gilbert and other syndromes with increased indirect bilirubin are allowed); serum transaminases must be less than two times the upper limit of normal
- •Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb), forced expiratory volume-one second (FEV1), forced vital capacity (FVC) must be greater than 50% predicted
- •Cardiac: Left ventricular ejection fraction at rest must be greater than 50%
- •Renal: Creatinine clearance (measured or calculated) must be equal or greater than 50 ml/min/1.73m^2
排除标准
- •Anti thymocyte globulin (ATG) or anti T cell therapy in prior 45 days
- •Splenectomized patients;
- •A positive pregnancy test administered to all females of childbearing potential prior to allogeneic stem cell transplant
- •Inability to comply with follow up as determined by the patient's physician
- •HIV-I/II infection prior to hematopoietic stem cell (HSC) transplantation, confirmed by nucleic acid test (NAT)
- •Uncontrolled bacterial or fungal infection
- •History of documented invasive aspergillosis or cytomegalovirus (CMV) pneumonia
- •Presence of any of the following comorbid conditions:
- •History of myocardial infarction
- •Congestive heart failure (even if symptomatically controlled)
- •Peripheral vascular disease (including intermittent claudication or history of bypass for arterial insufficiency)
- •Untreated thoracic or abdominal aneurysm (6cm or more)
- •History of any cerebrovascular accident including transient ischemic attacks
- •History of peptic ulcer disease requiring treatment
- •Connective tissue/rheumatologic disorders
- •Diabetes unless being managed with dietary changes only
- •Hemiplegia/paraplegia
- •History of solid tumor excluding skin or cervical carcinoma after curative resection
研究组 & 干预措施
First Study Stage: Study Treatment
Visilizumab, Tacrolimus and Methotrexate.
干预措施: Visilizumab (Drug)
First Study Stage: Study Treatment
Visilizumab, Tacrolimus and Methotrexate.
干预措施: Tacrolimus (Drug)
First Study Stage: Study Treatment
Visilizumab, Tacrolimus and Methotrexate.
干预措施: Methotrexate (Drug)
Second Study Stage: Standard Treatment
Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
干预措施: Antithymocyte globulin (ATG) (Drug)
Second Study Stage: Standard Treatment
Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
干预措施: Tacrolimus (Drug)
Second Study Stage: Standard Treatment
Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
时间窗: 100 days
Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned. Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II
次要结局
- Incidence of Epstein-Barr Virus (EBV) Reactivation(3 months)
- Incidence of Rituximab Response to Reactivated EBV Without PTLD(100 days)
- Overall Survival (OS)(At 2 years and 5 years)
- Pharmacodynamics of Visilizumab - Test 1(At 1 - 2 hours)
- Pharmacodynamics of Visilizumab - Test 2(Up to 205 hours)