A Multi-center Phase I/II Trial of Memory T Cell Donor Lymphocyte Infusions After Transplantation of CliniMACS® TCRα/β and CD19 Depleted Stem Cell Grafts From Haploidentical Donors for Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Phase I, dose escalation
研究概览
简要总结
The purpose of this clinical trial is to examine safety and toxicity of CD45RA depleted donor lymphocyte infusion (DLI) after transplantation of TCRα/β/CD19 depleted peripheral blood stem cells.
详细描述
Patients will undergo routine reduced intensity conditioning regimen and intravenous infusion of T-cell receptor alpha/beta (TCRα/β)/CD19 depleted peripheral blood stem cells (not content of clinical trial).
If no graft-versus-host disease (GVHD) occurs, patients receive the trial-related memory T cell donor lymphocyte infusion (DLI) on Day 30 after transplantation.
In a dose finding part (phase I) escalating doses will be applied in cohorts of three (three plus three design) patients with a maximum of 18 patients for three dose levels (dose level 1-3). A fourth lower dose level (dose level 0) is started, if >=2 out of 6 patients with dose level 1 develop aGVHD III/IV. The maximum tolerated dose (MTD) will be used for the confirmatory part (phase II) of the study.
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
- 8 Weeks 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult and pediatric patients with hematological malignancies in complete remission (CR), partial remission (PR) or with stable disease
- •Acute myeloid leukemia (AML):
- •Patients with high-risk AML in first complete remission (CR1)
- •Patients with relapsed or primary therapy-refractory AML
- •Acute lymphoid leukemia (ALL):
- •Patients with high-risk ALL in CR1
- •Patients with relapsed or primary refractory ALL
- •Hodgkin's disease: Patients with relapsed or primary refractory Hodgkin's disease
- •Non-Hodgkin's lymphoma: Patients with relapsed or primary refractory Non- Hodgkin's lymphoma
- •Myelodysplastic Syndrome (MDS)/ Myeloproliferative Syndrome (MPS):
- •°Patients with refractory MDS/MPS
- •Multiple myeloma (MM): Patients with relapsed or refractory multiple myeloma
排除标准
- •Age >65 years or <8 weeks
- •Patients with progressive disease prior hematopoietic cell transplantation (HCT)
- •<3 months after preceding HCT
- •Treatment with T-cell or Interleukin-2 (IL-2) targeted medication (e.g. alemtuzumab, basiliximab) within 60 days prior to study product infusion
- •Treatment with prednisolone at >2 mg/kg/day (or equivalent dosing of alternative glucocorticosteroids) at time of study product infusion.
- •Known allergy/hypersensitivity to any component of the study product
- •Treatment with another investigational drug within one month before inclusion
- •History of neurological impairment (active seizures, severe peripheral neuropathy, signs of leukoencephalopathy, active Central Nervous System (CNS) infection) Note: For patients with heavy pretreatment with irradiation or intrathecal chemotherapy pre-transplant CNS MRI and neurological consultation are mandatory.
- •Fungal infections with radiological and clinical progression
- •Liver function abnormalities with bilirubin >2 mg/dL and elevation of transaminases higher than 400 U/L
- •Chronic active viral hepatitis
- •Ejection fraction <40% or Shortening fraction <20% on echocardiography. Patients with > grade II hypertension by Common Toxicity Criteria (CTC)
- •Creatinine clearance below threshold defined for stem cell transplantation according to local clinical standard
- •Respiratory failure necessitating supplemental oxygen
- •HIV infection
- •Female patients who are pregnant or breast feeding, or adults of reproductive potential not willing to use an effective method of birth control during study treatment and for at least 12 months thereafter Note: Women of childbearing potential must have a negative serum pregnancy test at study entry.
- •Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which by assessment of the treating physician could compromise participation in the study
- •Patients with a history of psychiatric illness or a condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction)
- •Patients unwilling or unable to comply with the protocol or unable to give informed consent
研究组 & 干预措施
Single-arm
Donor lymphocytes from allogeneic donors depleted of CD45RA lymphocytes.
干预措施: CD45RA depleted donor lymphocyte infusion (DLI) (Biological)
结局指标
主要结局
Phase I, dose escalation
时间窗: 100 days
Safety and toxicity of CD45RA depleted DLI as defined by infusional toxicities and acute GVHD grad III-IV.
Phase II, extension phase
时间窗: 100 days
Acute graft-versus-host disease grade III-IV defined as GVHD occurring within 100 days after HCT
次要结局
未报告次要终点