A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Feasibility of haploidentical HSCT
研究概览
简要总结
This is a phase I study designed to determine the feasibility of transplantation using a novel transplant approach that employs a two-stage haploidentical cell infusion following myeloablative conditioning. This strategy, which includes selective depletion of naïve T cells, may speed immune reconstitution thereby potentially reducing the limitations of traditional haploidentical hematopoietic stem cell transplantation (HSCT) and increasing its potential therapeutic application. Additionally, the investigators intend to explore overall survival, event-free survival, hematopoietic cell recovery and engraftment as well as infection rates and complications in these patients.
详细描述
Twelve participants and 12 donors will be enrolled on this study. Donors will undergo seven days of hematopoietic stem cell (HSC) mobilization followed by two apheresis collections. Each apheresis collection will be processed by the CliniMACS system.
DONORS: A mobilization regimen of granulocyte colony stimulating factor (G-CSF) will be used to obtain a peripheral blood stem cell (PBSC) product from the donor. Apheresis will be performed for a minimum of two consecutive days, including one day for each cell product delivered.
STUDY PARTICIPANTS: Participants will undergo a two-stage haploidentical cell infusion following myeloablative conditioning. The first cell infusion will be a CD3-depleted product and the second infusion will be a CD45RA-depleted product.
Primary Objective:
- To determine the feasibility of haploidentical HSCT using two infusions engineered by negative selection on the Miltenyi CliniMACS system- the first by selective depletion of CD3+ cells, followed by a second depleted of CD45RA+ cells, in children with relapsed or refractory solid tumors or lymphomas.
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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Transplant Recipients:
- •At least 2 years of age and less than or equal to 21 years of age.
- •Histologically confirmed solid tumor or lymphoma at original diagnosis:
- •Ewing Sarcoma Family of Tumors (ESFT)
- •Gastrointestinal tumors
- •Germ Cell tumors
- •Hepatic tumors (including hepatocellular carcinoma and hepatoblastoma)
- •Lymphoma (including Hodgkin and non-Hodgkin lymphoma)
- •Kidney tumors (including Wilms tumor, rhabdoid tumors, clear cell carcinoma, and renal cell carcinoma)
- •Neuroblastoma
- •Soft tissue sarcoma (including rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma)
- •Malignancy has no reasonable expectation of cure with available alternative salvage therapy.
- •Has a suitable human leukocyte antigen (HLA) haploidentical donor available.
- •At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy.
- •Has recovered from all acute NCI Common Toxicity Criteria grade II-IV acute non-hematologic toxicities from prior therapy per the judgment of the PI.
- •Shortening fraction greater than or equal to 25%.
- •Creatinine clearance or glomerular filtration rate (GFR) greater than or equal to 50 mL/min/1.73 m
- •Pulse oximetry greater than or equal to 92% on room air
- •Alanine aminotransferase (ALT) and aspartate transaminase (AST) less than or equal to3 times the upper limit of the institution-established normal range.
- •Direct bilirubin less than or equal to 3.0 mg/dL.
- •Karnofsky or Lansky performance score of greater than or equal to 50.
排除标准
- •Transplant Recipients:
- •Newly diagnosed patients with no prior attempt at curative therapy.
- •Any primary or active central nervous system (CNS) malignancy, including metastatic disease.
- •Any active or prior malignant or pre-malignant condition of the bone marrow, excluding metastasis of the primary malignancy.
- •Prior allogeneic hematopoietic stem cell transplant.
- •Prior autologous stem cell transplant within previous 3 months.
- •Allergy to murine products or positive human anti-mouse antibody (HAMA).
- •(Female only) Known pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
- •(Female only) Breast feeding.
- •Inclusion Criteria - Donors:
- •At least 18 years of age.
- •Partially HLA matched family member.
- •Human immunodeficiency virus (HIV) negative.
- •Exclusion Criteria - Donors:
- •(Female only) Known pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
- •(Female only) Breast feeding.
研究组 & 干预措施
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: alemtuzumab (Drug)
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: fludarabine (Drug)
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: sirolimus (Drug)
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: Busulfan (Drug)
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: melphalan (Drug)
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: stem cells (Biological)
Treatment
Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.
Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.
Cells for infusion are prepared using the CliniMACS System.
干预措施: CliniMACS (Device)
结局指标
主要结局
Feasibility of haploidentical HSCT
时间窗: 30 days post transplantation
Feasibility is defined as engraftment (ANC≥ 500/mm3 for 3 consecutive tests performed on different days) evaluated before day +30.
次要结局
- hematopoietic cell recovery and engraftment rates(30 days post transplantation)
- overall survival (OS)(up to 1 year after transplantation)
- event-free survival(up to 1 year after transplantation)
- infection rates and complications(up to 5 years)