A Novel TBI Free Conditioning Protocol for Haploidentical Hematopoeitic Stem Cell Transplant in Acquired Aplastic Anemia
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of Participants with overall survival
研究概览
简要总结
Severe and very severe aplastic anemia are life threatening disorders for which allogeneic stem cell transplant is only curative treatment. However, matched sibling donor (MSD) is available in only 25-35% cases. Pakistan has a population of around 203 million but there is no donor registry available so there is no option available for matched unrelated donor (MUD) transplants . Haploidentical transplant represents only curative option for patients lacking MSD. Protocols involving post transplant cyclophosphamide require Total body irradiation (TBI) and utilize peripheral blood stem cell(PBSC) as graft source. TBI is not available in most of transplant centres across Pakistan due to lack of availability , cost and lack of expertise. The investigators have conceived a novel TBI free conditioning regimen to be used for haplo-identical Hemtopoeitic stem cell transplant in acquired aplastic anemia patients
详细描述
Aplastic anemia is considered to be a rare and heterogenous disease with incidence of 1-2 per million in western countries. Data from Asian studies show a 3-4 fold higher incidence.Majority of newly diagnosed aplastic anemia patients are younger and in Armed forces bone marrow transplant cohort of 1324 patients 64 % patient are younger than 24 years of age and 87% patients younger than 40 years (unpublished data).There is no donor registry in Pakistan and patients lacking sibling match donor cannot proceed to stem cell transplant due lack of matched unrelated donors. Horse antithymocyte globulin is not available currently in Pakistan and response to Rabbit antithymocyte globulin is dismal as shown in number of international studies. So haploidentical stem cell transplant remains only curative option for patients lacking Matched sibling donor. Currently there are 2 major platforms used for haplo-identical stem cell transplant. Post transplant cyclophosphamide based using TBI and haplo regimen of Peking university. TBI is not available for most of our patients in Pakistan due to cost,non-availability and lack of expertise. The investigators have formulated a novel TBI free regimen incorporating Busulphan, antithymocyte globulin and using co-primed bone marrow and peripheral blood harvest to minimize graft-versus-host disease and facilitate engraftment. Post transplant cyclophosphamide, Cyclosporine and mycophenolate mofetil will be used for graft-versus-host disease prophylaxis
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
- 2 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >2 years and < 60 years
- •Karnofsky performance status >= 70%
- •Aplastic Anemia that meets the following criteria:
- •i. Peripheral Blood (must fulfill 2 of 3): ii. <500 neutrophils iii. <20,000 platelets iv. absolute reticulocyte count <40,000/microL
- •Bone Marrow (must be ): markedly hypocellular (<25% of normal cellularity) with absence of reticulin and abnormal infiltrate
排除标准
- •Presence of donor specific antibodies
- •Fanconi anemia
- •Cytogenetic abnormalities suggestive of myelodysplastic syndrome
- •Prior HSCT
- •Human immunodeficiency virus infection
- •Active Hepatitis B virus infection
- •Active /uncontrolled bacterial, viral , fungal infection or Tuberculosis
- •Psychiatric illness
- •Poor cardiac function (ejection fraction <40%)
- •Poor pulmonary function (Forced vital capacity <50% predicted)
- •Poor liver function (bilirubin >= 2mg/dL)
- •Poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40)
研究组 & 干预措施
TBI free Haploidentical HSCT
Recipients will receive a reduced intensity conditioning regimen of ''Fludarabine'' 30 mg/m2 IV daily from day -7 to -3, ''Cyclophosphamide'' 14.5-30 mg/kg IV daily on day -6 and -5 , ''rabbit Antithymocyte globulin'' 5 mg /kg/day from day -6 to day-3; ''Busulphan'' IV 3.2 mg per kg/day in 02 divided doses on day -3 and day-2, ''Granulocyte Colony Stimulating factor primed Bone marrow harvest'' and/OR ''PBSC'' graft on day 0 and day +1 respectively and Graft versus host disease prophylaxis with ''post-transplant cyclophosphamide'' administered at a dose of 50mg/kg/day given daily on days +3 and +5 post-transplant and ''cyclosporine'' from day +5, ''mycophenolate mofetil'' from day+5 to day+35.
干预措施: Haploidentical HSCT using TBI free regimen, ''ATG'' with ''Post transplant cyclophosphamide'' (Drug)
结局指标
主要结局
Number of Participants with overall survival
时间窗: from the date of transplant to 1 year post transplant
overall survival is defined as the time interval from date of transplant to death or to last follow-up, whichever occurs first.
次要结局
- Frequency of Graft versus host disease(from the date of transplant to acute upto 100 day post transplant, chronic >100 days post transplant)
- Rate of Complications(from the date of transplant to 1 year from day of transplantation)
- Number of Participants with Disease free survival(from the date of transplant to 1 year post transplant)
- Time of Neutrophil engraftment(from the date of transplant to 10 to day 28 post transplant)