Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 264
- 试验地点
- 1
- 主要终点
- Disease Free Survival
研究概览
简要总结
The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.
详细描述
The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have Cancer and Leukemia Group B (CALGB) performance status (PS) 0, 1, or 2; must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide peripheral blood stem cells (PBPCs) and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have their diagnosis confirmed at the transplant center.
- •Performance status must be Cancer and Leukemia Group B (CALGB) = 0, 1, or
- •Subjects must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 or better allele level match matched unrelated donor (MUD) (at A,B, C, DRB1, DQ).
- •HIV negative.
- •Women of child bearing potential must have a negative pregnancy test within 1 week of starting therapy.
- •Subjects > or equal to 18 years of age are eligible.
- •Subjects must have a Multi Gated Acquisition Scan (MUGA) and/or Echocardiography (ECHO) or cardiac magnetic resonance (MR) and or diffusing capacity testing of the lung for carbon monoxide (DLCO) performed before transplant.
- •Specific populations:
- •Group A) Subjects with a high chance of progressive lymphoid or myelomatous diseases.
- •Group B) Subjects with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders
排除标准
- •Pregnant or lactating women.
- •Subjects with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
- •Subjects with uncontrolled, progressive infections.
- •Subjects who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
- •Subjects with active central nervous system (CNS) disease.
- •Donor Inclusion Criteria:
- •Donor must be capable of providing informed consent. If 14-17 years of age, a 'single patient exemption' from the local Institutional Review Board must be obtained.
- •Donor must not have any medical condition which would make mobilization or apheresis more than a minimal risk, and should have the following:
- •Adequate cardiac function by history and physical examination. Those with a history of cardiac failure or infarction should be evaluated by a cardiologist prior to donation
- •Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of 3000, and platelets 100,
- •Females should not be pregnant or lactating and have a negative serum pregnancy test within 1 week of beginning mobilization if of child bearing potential.
研究组 & 干预措施
Cohort A - Lymphoid Disease
Group A: Patients with a high chance of progressive lymphoid or myelomatous disease undergo Non-myeloablative Stem Cell Transplantation.
干预措施: Non-myeloablative Stem Cell Transplantation (Drug)
Cohort B - Myeloid Disease
Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders undergo Non-myeloablative Stem Cell Transplantation.
干预措施: Non-myeloablative Stem Cell Transplantation (Drug)
结局指标
主要结局
Disease Free Survival
时间窗: 2 years
Estimate disease free survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. DFS was defined as the period of time between the day of transplantation and either disease relapse or death due to the disease. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants who were disease free at 2 years is reported by donor type.
次要结局
- Graft Failure(180 days)
- Immune Recovery(1 year)
- Progression Free Survival(2 years)
- Overall Survival(2 years)
研究者
David Rizzieri, MD
Associate Professor of Medicine
Duke University