Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies
Haploidentical Hematopoietic Stem Cell Transplantation Utilizing Partial T-Cell Depletion as Immunotherapy for Hematologic Malignancies
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor.
Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality.
Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives.
This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.
研究概览
地位
详细说明
Secondary outcome evaluations for this clinical study included the following:
- To estimate one-year overall survival for research participants with high risk malignancies who receive a haploidentical HSCT
- To compare overall survival and cumulative incidence of relapse for the two groups of patients with their corresponding historical controls
- To estimate disease-free survival and event-free survival in participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of overall grade 3-4 acute GvHD in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of chronic GvHD and graft failure in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the incidence of non-hematologic regimen-related toxicity and regimen-related mortality in the first 100 days post-transplant in research participants with hematologic malignancies who receive a haploidentical HSCT
- To estimate the number of research participants who develop evidence of EBV reactivation or post-transplant lymphoproliferative disease (PTLPD)
- To describe disease-free survival, GvHD and engraftment in research participants receiving grafts from Killer immunoglobulin-like receptor (KIR) mismatched and KIR matched haploidentical donors
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Tennessee
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Memphis、Tennessee、美国、38105
- St. Jude Children's Research Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Eligible participants were assigned to one of two different strata dependent on diagnosis, disease status and/or past transplant experience. Both strata received the same intervention but will be followed and analyzed separately.
Group A must have one of the following diagnosis
- Acute lymphoid leukemia (ALL) in second or subsequent remission or high risk in first remission
- Acute myeloid leukemia (AML) in remission or with ≤ 25% blasts in bone marrow
- Chronic myeloid leukemia (CML)
- Juvenile myelomonocytic leukemia (JMML)
- Myelodysplastic syndrome (MDS)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) in second or subsequent remission after autologous HSCT, or unable to have hematopoietic stem cells collected for autologous HSCT
Group B must have one of the following refractory diagnosis (chemoresistant relapse or primary induction failure)
- Acute lymphoid leukemia (ALL)
- Acute myeloid leukemia (AML) ≥ 25% blast in bone marrow
- Secondary AML / MDS
- Chronic myeloid leukemia (CML) in accelerated phase or blast crisis
- Juvenile myelomonocytic leukemia (JMML)
- Myelodysplastic syndrome (MDS)
- Hodgkin's (HD) or non-Hodgkin's lymphoma (NHL) with residual disease followed by autologous HSCT or who have chemo-resistant disease
- Or patients who have undergone prior allogeneic HSCT or who have a co-morbid condition that in the medical opinion of the Transplant Faculty makes standard myeloablation prohibited
- At least 2 and less than or equal to 21 years of age
- Lacks suitable HLA-identical sibling or matched available unrelated donor and has a mismatched family member donor that is available, HIV negative and at least 18 years old
- Cardiac shortening fraction ≥ 25%
- Creatinine clearance ≥ 40 cc/min/1.73m^2
- FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air
- Direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L
- Karnofsky or Lansky (age dependent) performance score of ≥ 50
Exclusion Criteria:
- Known allergy to murine products
- Lactating (female patient)
- Pregnancy (female patient)
- Active central nervous system (CNS) leukemia
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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其他:1个
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Systemic chemotherapy and antibodies as follows: Transplant recipients received a reduced intensity conditioning regimen consisting of OKT-3, fludarabine, thiotepa, and melphalan followed by an infusion of a T-cell depleted haploidentical hematopoietic stem cell graft. The antibody Rituximab was administered within 24 hours of the infusion in an effort to prevent PTLPD. In addition to T -cell depletion of the donor product, Mycophenylate mofetil was provided over several months as prophylaxis for GVHD
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device
Miltenyi Biotec CliniMACS stem cell selection device
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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To measure the rate of disease relapse by six months posttransplant in children and young adults with refractory hematologic malignancies who receive a haploidentical stem cell graft processed using the investigational CliniMACS cell sorting device.
大体时间:September 2006
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September 2006
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合作者和调查者
调查人员
- 首席研究员:Gregory Hale, M.D.、St. Jude Children's Research Hospital
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- HAPREF
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急性髓性白血病的临床试验
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