Prophylaxis of the Graft-Versus-Host-Disease in Patients After Allogeneic Stem Cell Transplantation With a Combination of Tacrolimus and Everolimus
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Incidence of acute GvHD grade III and IV within the first 100 days after the stem cell transplantation
研究概览
简要总结
The purpose of this pilot study is to provide preliminary data about the efficacy and the safety of the combination of tacrolimus with everolimus in the prophylaxis of the graft-versus-host-disease (GvHD) in patients after allogeneic stem cell transplantation.
详细描述
The allogeneic stem cell transplantation is a successful therapeutic approach in the treatment of a number of hematologic diseases. Nevertheless, it is associated with substantial risks and complications. A major life-threatening complication that occurs in the post transplantation period is the graft versus host disease, especially its severe forms (Grade III and Grade IV). For this reason, a combined immunosuppressive therapy is standard in patients after a stem cell transplantation. In this regard, the combination between cyclosporin A and methotrexate in the prevention of GvHD has been particularly successful. However, the incidence rate of GvHD and consequent mortality are still fairly high. Besides, the therapy itself is accompanied by serious side effects. Therefore, there is a need for a more efficient, less toxic, combined immunosuppressive therapy. The purpose of this pilot study is to test a new combination of immunosuppressives (tacrolimus and everolimus) for the prevention of GvHD after an allogeneic stem cell transplantation. Tacrolimus is a macrolide immunosuppressant that acts as a calcineurin inhibitor, thereby preventing the activation and proliferation of the T-lymphocytes. Everolimus is a semisynthetic macrocyclic lactone that inhibits the activity of a key protein involved in the regulation of the cell cycle, the so called m-TOR protein. Both medicaments act complementary and potently inhibit the proliferation of immune cells. Previous studies have shown that the combination of tacrolimus with everolimus decreases significantly the rejection rate after solid organ transplantation and this combination is generally well tolerated.
This study is designed as a prospective, single-center, non-randomized, open-label non-controlled pilot study. Study related visits are scheduled to take place at regular time intervals and the patients will be followed up to one year after the stem cell transplantation. The study is designed and will be conducted in accordance with the ICH-GCP guidelines and the respective national and international laws.
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
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients between 18 and 70 years of age
- •Planned allogeneic stem cell transplantation either from a related or an unrelated donor
- •Written informed consent
排除标准
- •Previous stem cell transplantation
- •Use of antibody Campath (anti CD-52) or ATG during the conditioning
- •In vitro T-cell depleted graft
- •Known hypersensitivity to everolimus or other constituents of the study medication
- •Symptomatic infectious disease
- •Hepatic disease (ASAT > 2 x ULN)
- •Renal insufficiency (creatinine > 2 x ULN)
- •HIV infection
- •Life expectancy < 3 months
- •Severe lung disease (FEV1 < 50% of the normal value)
- •Severe psychiatric disorder
- •Subjects unlikely to comply with the requirements of the protocol
- •Known or current alcohol, medication or drug abuse
- •Pregnancy or lactation
- •Women of child-bearing potential without reliable contraception unless they meet the following criteria: postmenopausal (12 months of natural amenorrhea);postoperation status (6 weeks after surgical bilateral oophorectomy with or without hysterectomy);use of highly effective birth control method (defined as one which results in a low failure rate i.e. less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomized partner)
- •Men that do not use one of the following methods for prevention of conception:sexual abstinence; condom; vasectomy
- •Participation of the subject in another clinical trial within the last 4 weeks
结局指标
主要结局
Incidence of acute GvHD grade III and IV within the first 100 days after the stem cell transplantation
时间窗: first 100 days
次要结局
- Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0)(within 100 days after Tx)
- Hypersensitivity reactions(within 56 days after Tx)
- Thrombotic thrombocytopenic purpura(within 56 days after Tx)
- Hyperlipidemia(within 56 days after Tx)
- Total and relapse-free survival rate one year after the stem cell transplantation