Phase I Dose Escalation of T-cell Receptor α/β Depleted Donor Lymphocyte Infusions Following CD34+- Selected Allogeneic Stem Cell Transplantation From Related & Unrelated Donors in Patients With Lymphoid, Myeloid or Plasma Cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs)
研究概览
简要总结
This pilot study is being conducted to treat patients who have a certain type of malignancy (lymphoid or myeloid) with immune effector cells after a T-cell depleted allogeneic hematopoietic cell transplantation (TCD HSCT).
This study is designed to see whether an investigational cellular product of immune cells obtained from a donor's cells that have been treated so that the type of cells that can lead to graft vs host disease have been removed can be safely administered. These cell products are administered following the initial stem cell transplant to assess the effect and improvement on minimal residual disease status, infectious complication, progression-free and overall survival.
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with hematologic malignancies that are candidates CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation.
- •Patients must have a Karnofsky (adult) Performance Status of at least 70%.
- •Patients must have adequate organ function measured by:
- •Cardiac: asymptomatic or if symptomatic then left ventricular ejection fraction (LVEF) at rest must be 50% and must improve with exercise.
- •Hepatic: < 3x upper limit of normal (ULN) AST and < 1.5 mg/dL total serum bilirubin, unless there is congenital benign hyperbilirubinemia. Patients with higher bilirubin levels due to causes other than active liver disease is also eligible with Pl approval (e.g., patients with PNH, Gilbert's disease or other hemolytic disorders).
- •Renal: serum creatinine: ≤ 1.2 mg/dL or if serum creatinine is outside the normal range, then creatinine clearance (CrCl) > 40 mL/min (measured or calculated/estimated).
- •Pulmonary: asymptomatic or if symptomatic, diffusing capacity of the lungs for carbon monoxide (DLCO) 50% of predicted (corrected for hemoglobin).
- •Each patient must be willing to participate as a research subject and must sign an informed consent form.
排除标准
- •Patients with active acute GvHD.
研究组 & 干预措施
HLA Matched Cohort I
5 x 10^5/kg at 6-7 weeks post-transplant (Group A), 4-5 weeks post-transplant (Group B), or 2-3 weeks post-transplant (Group C)
干预措施: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions (Biological)
HLA Matched Cohort II
5 x 10^5/kg starting time point X (whichever was safest as determined by Matched Cohort I), 1 x 10^6/kg 3-4 weeks after first dose, and 1 x 10^6/kg 3-4 weeks after second dose
干预措施: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions (Biological)
HLA Matched Cohort III
5 x 10^5/kg starting time point X (whichever was safest as determined by Matched Cohort I), 1 x 10^6/kg 3-4 weeks after first dose, and 2 x 10^6/kg 3-4 weeks after second dose
干预措施: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions (Biological)
HLA Mismatched Cohort I
1 x 10^5/kg at 6-7 weeks post-transplant (Group A), 4-5 weeks post-transplant (Group B), or 2-3 weeks post-transplant (Group C)
干预措施: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions (Biological)
HLA Mismatched Cohort II
1 x 10^5/kg starting time point Y (whichever was safest as determined by Mismatched Cohort I), 5 x 10^5/kg 3-4 weeks after first dose, and 5 x 10^5/kg 3-4 weeks after second dose
干预措施: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions (Biological)
HLA Mismatched Cohort III
1 x 10^5/kg starting time point Y (whichever was safest as determined by Mismatched Cohort I), 5 x 10^5/kg 3-4 weeks after first dose, and 1 x 10^6/kg 3-4 weeks after second dose
干预措施: T-cell Receptor α/β Depleted Donor Lymphocyte Infusions (Biological)
结局指标
主要结局
Incidence of Treatment-emergent Serious Adverse Events (TE-SAEs)
时间窗: 30 days post-infusion
TE-SAEs are defined as the composite of death, non-fatal pulmonary embolism, stroke, acute graft versus host disease (GvHD), and clinically significant laboratory test abnormalities.
次要结局
- Number of Participants in Remission(2 years)
- Number of Participants With Transplant-associated Viral Complications(2 years)
- Disease Free Survival- Measured by Absence of Relapse/Recurrence or Death.(2 years)
- Overall Survival(2 years)
研究者
Guenther Koehne
Deputy Director and Chief of Blood and Marrow Transplant, Hematologic Oncology and Benign Hematology
Baptist Health South Florida