Randomized Comparison of Cyclophosphamide Versus Fludarabine in Addition to Anti-thymocyte Globulin for the Conditioning Therapy in Allogeneic Hematopoietic Cell Transplantation for Adult Acquired Aplastic Anemia
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- regimen-related toxicities(RRT)
研究概览
简要总结
The purpose of this study is to reduce the regimen related toxicities and transplantation related mortality after allogeneic stem cell transplantation in adult acquired aplastic anemia (AA), the trials of reduced dose of Cy along with fludarabine and ATG were performed.11-21 The investigators preliminary data of randomized comparison of cyclophosphamide plus fludarabine versus cyclophosphamide alone in addition to anti-thymocyte globulin for the conditioning therapy in allogeneic hematopoietic cell transplantation for bone marrow failure syndrome supports reduced dose of Cy along with fludarabine and ATG.
Conditioning regimen without Cy may reduce RRT because Cy-containing conditioning remains several RRT such as hemorrhagic cystitis, SOS and graft versus host disease (GvHD). Recently there were small trials of fludarabine and ATG (Flu-ATG) for the conditioning regimen of alloHSCT.22-24 These data raised the feasibility of fludarabine and ATG without Cy for patients with AA.
This new conditioning regimen of Flu-ATG will be compared to standard regimen of Cy- ATG in a randomized controlled trial.
详细描述
TREATMENT PLAN
- The patients will be admitted to laminar air flow room.
- The patients will have triple lumen Hickman central venous catheter (CVC) placed. Chest X-ray should be taken after CVC placement to confirm the location of CVC and absence of pneumothorax.
- Menstruating women will be given norethindrone (Primolut) 10 mg po daily.
- The preparatory regimen is as follows:
Conditioning therapy will start on day -5 in patients who are randomized to receive Cy+ATG. Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -5. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter. Mesna 12 mg/kg iv push immediately before Cy and 3, 6, 9, and 12 hours after Cy. Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2. Premedication for ATG (ALG) will include methylprednisolone 2 mg/kg iv infusion, Tylenol 600 mg po, and Avil 45.5 mg iv push. The doses of cyclophosphamide and ATG (ALG) will be calculated using actual body weight.
Conditioning therapy will start on day -7 in patients who are randomized to receive Flu-ATG. Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 6 consecutive days (days -7 to -2). Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2. Premedication for ATG (ALG) will include methylprednisolone 2 mg/kg iv infusion, Tylenol 600 mg po, and Avil 45.5 mg iv push. The doses of cyclophosphamide and ATG (ALG) will be calculated using actual body weight. 2. GVHD prophylaxis will include cyclosporine plus methotrexate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe aplastic anemia
- •Severe aplastic anemia (SAA) is defined as a hypocellular bone marrow (cellularity<25%) and two or more of the following: granulocyte count <500/ml, platelet count <20,000/ml, and corrected reticulocyte count <1.0%
- •Very severe aplastic anemia (VSAA) is defined as the criteria for SAA plus a granulocyte count <200/ml
- •Patients should be 15 years of age or older, but younger than 65 years.
- •The performance status of the patients should be 70 or over by Karnofsky performance scale (see Appendix I).
- •Patients must have adequate hepatic function (bilirubin less than 2 mg/dl, AST and ALT less than three times the upper normal limit)
- •Patients must have adequate renal function (creatinine less than 2.0 mg/dl).
- •Patients must have adequate cardiac function (ejection fraction > 45% on echocardiogram).
- •Exclusion criteria:
- •Patients should not have major illness or organ failure.
- •Patients must not have a psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlikely, and making informed consent impossible.
- •Patients must not be in pregnancy.
- •Hypoplastic myelodysplastic syndrome
- •Paroxysmal nocturnal hemoglobinuria
排除标准
- 未提供
研究组 & 干预措施
CY-ATG(Arm1)
Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -5. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter.
Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2
干预措施: Cy-ATG (Drug)
Flu-ATG(Arm2)
Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 6 consecutive days (days -7 to -2) Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2
干预措施: Flu-ATG (Drug)
结局指标
主要结局
regimen-related toxicities(RRT)
时间窗: 7 years
* The RRTs will be evaluated in terms of mucositis, hemorrhagic cystitis, SOS, acute graft versus host disease (GvHD), infection rate, graft failure, time to engraftment. * Overall feasibility will be evaluated by RRTs, time to engraftment, chronic GvHD, treatment-related mortality (TRM), relapse rate, infertility, chimerism status, changes of hemostatic variables, event-free survival and overall survival.
次要结局
- Overall feasibility(7 years)
研究者
Yae Eun Jang
Research nurse
Cooperative Study Group A for Hematology