非恶性疾病患者的低强度训练 (RIC) 方案 (RIC)
2026年6月23日 更新者：Children's Hospital of Philadelphia
这是一项 II 期试点研究，旨在评估非恶性疾病患者在非恶性疾病同种异体移植的情况下使用强度降低的调节方案的植入和毒性。 骨髓或脐带血可以作为干细胞来源。
最近，降低强度调节 (RIC) 方案已用于成年白血病患者和非恶性疾病的儿科患者。 这些方案的耐受性更好，导致移植相关的发病率和死亡率更低。 稳定的混合嵌合体虽然不足以根除白血病，但可能足以治愈非恶性疾病患者。
研究概览
详细说明
该方案中有两种针对 6 个月以上儿童的预处理方案。 使用阿仑单抗（Campath）、氟达拉滨和美法仑。 这些方案因 Alemtuzumab (Campath) 的给药时间和剂量而异。 这两个时间是远端和中间。
- 在同种异体移植前 22 天开始远端露营。
- 同种异体移植前 14 天开始中间 campath。
针对 6 个月以下免疫缺陷儿童的预处理方案省略美法仑，代之以两天的白消安。 该方案已在英国成功应用，并成功用于费城儿童医院 (CHOP) 的一名 3 个月大的婴儿，该婴儿植入了单倍体相合供体。
研究类型
介入性
注册 (实际的)
56
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
-
Pennsylvania
-
Philadelphia、Pennsylvania、美国、19104
- The Children's Hospital of Philadelphia
-
-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
6个月 至 25年 (孩子、成人)
接受健康志愿者
不
描述
纳入标准：
- 年龄 >6 个月- 25 岁
适用于远端阿仑单抗的疾病：
- 免疫失调多发性内分泌病肠病 X 连锁 (IPEX) 综合征
- 镰状细胞性贫血症
- 重型地中海贫血
- 骨髓衰竭
适合中级阿仑单抗的疾病
- 噬血细胞性淋巴组织细胞增生症其他巨噬细胞活化综合征，重度朗格汉斯组织细胞增生症
- 严重联合免疫缺陷、腺苷脱氨酶缺乏、普通变异型免疫缺陷
- 维斯科特-奥尔德里奇综合征
器官标准：
- 心脏：超声心动图缩短分数 >27%
- 肾脏：血清肌酐低于年龄正常上限的 1.5 倍
- 肝脏：肝功能检查必须低于正常值上限的 5 倍
- 没有活动性感染
排除标准
1. 不受控制的细菌、真菌或病毒感染
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Reduced-Intensity Conditioning (RIC) HSCT
Participants receive reduced-intensity conditioning with alemtuzumab-, fludarabine-, and melphalan-based regimens, varying by timing of alemtuzumab (distal or intermediate).
Regimens are based on established protocols used in non-malignant disorders.
Alemtuzumab is administered prior to other agents to reduce risk of declining donor chimerism.
Participants then undergo allogeneic stem cell transplantation with standard post-transplant care.
|
A pre-transplant conditioning approach designed to provide sufficient immunosuppression to enable donor cell engraftment while minimizing regimen-related toxicity compared to myeloablative conditioning.
Regimens are adapted based on patient age and underlying disease characteristics using the following agents: Campath, Fludarabine, Melphalan, Cyclosporine, Cellcept (MMF).
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
植入
大体时间：移植后 -100 天
|
将使用强度降低的预处理方案评估非恶性疾病患者的植入
|
移植后 -100 天
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Event-free Survival
大体时间：1 year post transplant
|
Event-free survival is defined as the time interval to either primary or late graft failure, disease recurrence, or death.
|
1 year post transplant
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Timothy J Olson, MD、Children's Hospital of Philadelphia
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P, Chakraverty R, Marshall T, Osman H, Mahendra P, Craddock C, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood. 2002 Jun 15;99(12):4357-63. doi: 10.1182/blood.v99.12.4357.
- Marsh RA, Kim MO, Liu C, Bellman D, Hart L, Grimley M, Kumar A, Jodele S, Myers KC, Chandra S, Leemhuis T, Mehta PA, Bleesing JJ, Davies SM, Jordan MB, Filipovich AH. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Biol Blood Marrow Transplant. 2013 Nov;19(11):1625-31. doi: 10.1016/j.bbmt.2013.09.001. Epub 2013 Sep 10.
- Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ, Woolfrey A, Amylon M, Sullivan KM, Storb RF, Walters MC. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant. 2003 Aug;9(8):519-28. doi: 10.1016/s1083-8791(03)00192-7.
- Chakraverty R, Peggs K, Chopra R, Milligan DW, Kottaridis PD, Verfuerth S, Geary J, Thuraisundaram D, Branson K, Chakrabarti S, Mahendra P, Craddock C, Parker A, Hunter A, Hale G, Waldmann H, Williams CD, Yong K, Linch DC, Goldstone AH, Mackinnon S. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002 Feb 1;99(3):1071-8. doi: 10.1182/blood.v99.3.1071.
- Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD, Dalle JH, Di Bartolomeo P, de Heredia CD, Dickerhoff R, Giardini C, Gluckman E, Hussein AA, Kamani N, Minkov M, Locatelli F, Rocha V, Sedlacek P, Smiers F, Thuret I, Yaniv I, Cavazzana M, Peters C; EBMT Inborn Error and EBMT Paediatric Working Parties. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014 May;99(5):811-20. doi: 10.3324/haematol.2013.099747.
- Cooper N, Rao K, Gilmour K, Hadad L, Adams S, Cale C, Davies G, Webb D, Veys P, Amrolia P. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood. 2006 Feb 1;107(3):1233-6. doi: 10.1182/blood-2005-05-1819. Epub 2005 Oct 11.
- King AA, Kamani N, Bunin N, Sahdev I, Brochstein J, Hayashi RJ, Grimley M, Abraham A, Dioguardi J, Chan KW, Douglas D, Adams R, Andreansky M, Anderson E, Gilman A, Chaudhury S, Yu L, Dalal J, Hale G, Cuvelier G, Jain A, Krajewski J, Gillio A, Kasow KA, Delgado D, Hanson E, Murray L, Shenoy S. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015 Dec;90(12):1093-8. doi: 10.1002/ajh.24183. Epub 2015 Oct 6.
- Wildin RS, Smyk-Pearson S, Filipovich AH. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet. 2002 Aug;39(8):537-45. doi: 10.1136/jmg.39.8.537.
- Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, Shenoy S. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007 Jan 1;109(1):383-5. doi: 10.1182/blood-2006-05-025072. Epub 2006 Sep 21.
- Del Toro G, Satwani P, Harrison L, Cheung YK, Brigid Bradley M, George D, Yamashiro DJ, Garvin J, Skerrett D, Bessmertny O, Wolownik K, Wischhover C, van de Ven C, Cairo MS. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant. 2004 Mar;33(6):613-22. doi: 10.1038/sj.bmt.1704399.
- Kean LS, Durham MM, Adams AB, Hsu LL, Perry JR, Dillehay D, Pearson TC, Waller EK, Larsen CP, Archer DR. A cure for murine sickle cell disease through stable mixed chimerism and tolerance induction after nonmyeloablative conditioning and major histocompatibility complex-mismatched bone marrow transplantation. Blood. 2002 Mar 1;99(5):1840-9. doi: 10.1182/blood.v99.5.1840.
- Fischer A, Landais P, Friedrich W, Morgan G, Gerritsen B, Fasth A, Porta F, Griscelli C, Goldman SF, Levinsky R, et al. European experience of bone-marrow transplantation for severe combined immunodeficiency. Lancet. 1990 Oct 6;336(8719):850-4. doi: 10.1016/0140-6736(90)92348-l.
- Friedrich W, Goldmann SF, Vetter U, Fliedner TM, Heymer B, Peter HH, Reisner Y, Kleihauer E. Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow. Lancet. 1984 Apr 7;1(8380):761-4. doi: 10.1016/s0140-6736(84)91277-7.
- Klangsinsirikul P, Carter GI, Byrne JL, Hale G, Russell NH. Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood. 2002 Apr 1;99(7):2586-91. doi: 10.1182/blood.v99.7.2586.
- Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH, Mackinnon S, Hale G. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood. 2003 Jul 1;102(1):404-6. doi: 10.1182/blood-2002-09-2687. Epub 2003 Mar 6.
- Chakrabarti S, Avivi I, Mackinnon S, Ward K, Kottaridis PD, Osman H, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW. Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality. Br J Haematol. 2002 Dec;119(4):1125-32. doi: 10.1046/j.1365-2141.2002.03992.x.
- Shah AJ, Kapoor N, Crooks GM, Weinberg KI, Azim HA, Killen R, Kuo L, Rushing T, Kohn DB, Parkman R. The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and immune reconstitution in recipients of pediatric unrelated transplants. Biol Blood Marrow Transplant. 2007 May;13(5):584-93. doi: 10.1016/j.bbmt.2007.01.076. Epub 2007 Mar 23.
- Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ, Mohanakumar T, Rao A, Hayashi RJ. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant. 2005 Feb;35(4):345-52. doi: 10.1038/sj.bmt.1704795.
- Jacobsohn DA, Duerst R, Tse W, Kletzel M. Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet. 2004 Jul 10-16;364(9429):156-62. doi: 10.1016/S0140-6736(04)16628-2.
- Horn B, Baxter-Lowe LA, Englert L, McMillan A, Quinn M, Desantes K, Cowan M. Reduced intensity conditioning using intravenous busulfan, fludarabine and rabbit ATG for children with nonmalignant disorders and CML. Bone Marrow Transplant. 2006 Feb;37(3):263-9. doi: 10.1038/sj.bmt.1705240.
- Amrolia P, Gaspar HB, Hassan A, Webb D, Jones A, Sturt N, Mieli-Vergani G, Pagliuca A, Mufti G, Hadzic N, Davies G, Veys P. Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. Blood. 2000 Aug 15;96(4):1239-46.
- Rao K, Amrolia PJ, Jones A, Cale CM, Naik P, King D, Davies GE, Gaspar HB, Veys PA. Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. Blood. 2005 Jan 15;105(2):879-85. doi: 10.1182/blood-2004-03-0960. Epub 2004 Sep 14.
- Kikuta A, Ito M, Mochizuki K, Akaihata M, Nemoto K, Sano H, Ohto H. Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction. Bone Marrow Transplant. 2006 Nov;38(10):665-9. doi: 10.1038/sj.bmt.1705511. Epub 2006 Oct 2.
- Bhatla D, Davies SM, Shenoy S, Harris RE, Crockett M, Shoultz L, Smolarek T, Bleesing J, Hansen M, Jodele S, Jordan M, Filipovich AH, Mehta PA. Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome. Bone Marrow Transplant. 2008 Aug;42(3):159-65. doi: 10.1038/bmt.2008.151. Epub 2008 May 26.
- Parikh SH, Mendizabal A, Benjamin CL, Komanduri KV, Antony J, Petrovic A, Hale G, Driscoll TA, Martin PL, Page KM, Flickinger K, Moffet J, Niedzwiecki D, Kurtzberg J, Szabolcs P. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant. 2014 Mar;20(3):326-36. doi: 10.1016/j.bbmt.2013.11.021. Epub 2013 Dec 1.
- King A, Shenoy S. Evidence-based focused review of the status of hematopoietic stem cell transplantation as treatment of sickle cell disease and thalassemia. Blood. 2014 May 15;123(20):3089-94; quiz 3210. doi: 10.1182/blood-2013-01-435776. Epub 2014 Feb 7. No abstract available.
- Oshrine BR, Olson TS, Bunin N. Mixed chimerism and graft loss in pediatric recipients of an alemtuzumab-based reduced-intensity conditioning regimen for non-malignant disease. Pediatr Blood Cancer. 2014 Oct;61(10):1852-9. doi: 10.1002/pbc.25113. Epub 2014 Jun 17.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2008年1月1日
初级完成 (实际的)
2024年7月1日
研究完成 (实际的)
2025年6月1日
研究注册日期
首次提交
2010年1月15日
首先提交符合 QC 标准的
2010年1月15日
首次发布 (估计的)
2010年1月18日
研究记录更新
最后更新发布 (实际的)
2026年7月21日
上次提交的符合 QC 标准的更新
2026年6月23日
最后验证
2026年6月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.