A Phase II Study of Neovii Anti-human T-lymphocyte Immunoglobulin (ATLG, Grafalon®) With Post Transplant Escalated Doses of Post-transplant-Cyclophosphamide to Prevent Acute and Chronic GVHD Post Allogeneic Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Overal survival
研究概览
简要总结
Investigators hypothesize that combination of ATLG with PTCy in matched or mismatched unrelated hematopoietic stem cell transplantation will reduce acute and chronic GVHD incidence. Furthermore it will allow shortening of the length of post-transplantation immunosuppression with calcineurin inhibitor (CNI) administration (currently administrated in addition to ATG as GVHD prophylaxis in daily common practice)
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with MDS/AML
- •18 years or older and willing and able to comply with the protocol requirements.
- •LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
- •Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
- •Patients conditioned with reduced intensity or reduced toxicity conditioning of fludarabine with reduced dose (2 days) or myeloabalative doses (4 days) of busulfan or with treosulfan.
- •Patients must sign written informed consent.
- •Adequate birth control in fertile patients.
排除标准
- •Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
- •Patients with respiratory failure (DLCO < 30%).
- •Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
- •Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
- •Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
- •Creatinine > 2.0 mg/dl
- •ECOG-Performance status > 2
- •Uncontrolled infection
- •Pregnancy or lactation
- •CNS disease involvement
- •Pleural effusion or ascites > 1 liter.
研究组 & 干预措施
cyclophosphamide and ATLG
The study will include 2 phases. In the first phase escalated doses of post-transplant cyclophosphamide up to a maximal dose of 50 mg/kg administered on day +3 and +4 (target dose) will be added to a standard GVHD prophylaxis consisting of anti-human T-lymphocyte immunoglobulin (ATLG, Grafalon®, formerly ATG-Fresenius S, Neovii Pharmaceuticals) 15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation in order to find the maximally tolerated dose (MTD) of post-transplant cyclophosphamide (PTCy) in combination with pre-transplant immunosuppression by ATLG. The second phase will use the MTD cyclophosphamide dose identified in the first phase.
干预措施: Cyclophosphamide (Drug)
cyclophosphamide and ATLG
The study will include 2 phases. In the first phase escalated doses of post-transplant cyclophosphamide up to a maximal dose of 50 mg/kg administered on day +3 and +4 (target dose) will be added to a standard GVHD prophylaxis consisting of anti-human T-lymphocyte immunoglobulin (ATLG, Grafalon®, formerly ATG-Fresenius S, Neovii Pharmaceuticals) 15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation in order to find the maximally tolerated dose (MTD) of post-transplant cyclophosphamide (PTCy) in combination with pre-transplant immunosuppression by ATLG. The second phase will use the MTD cyclophosphamide dose identified in the first phase.
干预措施: anti-human T-lymphocyte immunoglobulin (ATLG) (Drug)
结局指标
主要结局
Overal survival
时间窗: 24 months
Overall survival will be calculated from the day of SCT until death or last follow-up. OS will be determined using Kaplan-Meyer product limit method.
Disease-free survival
时间窗: 24 months
Disease-free survival will be calculated from the day of SCT until relapse, death of any cause, or last follow-up. DFS will be determined using Kaplan-Meyer product limit method.
次要结局
未报告次要终点
研究者
Prof Arnon Nagler
M.D., M.Sc, Professor of Medicine Tel Aviv University, Director Hematology Division, Chair Israeli BMT Association,Chair of the ALWP of the EBMT, Co-Chair Scientific Council of the EBMT Chaim Sheba Medical Center
Sheba Medical Center