An Open-label, Uncontrolled, Multicenter, Multinational Study on the Efficacy and Safety of Administration of Donor Lymphocytes Depleted of Alloreactive T-cells (ATIR), Through the Use of TH9402 and Light Treatment in an ex Vivo Process, in Patients Receiving a CD34-selected Peripheral Blood Stem Cell Graft From a Related, Haploidentical Donor
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 40
- 试验地点
- 30
- 主要终点
- Transplant Related Mortality
研究概览
简要总结
The purpose of this study is to determine whether the administration of a donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) after a T-cell depleted stem cell transplant from a related, haploidentical donor enhances survival by improving the immune effect against infections while preventing graft-versus-host disease .
详细描述
Allogeneic stem cell transplantation is the treatment of choice for many patients with leukemia and other hematologic malignancies. However, a major limitation of this therapy is that for a significant number of patients no fully HLA-matched donor can be found. The application of partially HLA-matched (haploidentical) family donors, who are virtually always available, has some complications. If there is no T-cell add-back it increases the risk for life-threatening infections and disease relapse, while in case of T-cell add-back the risk for graft-versus-host disease is raised.
Kiadis Pharma has developed a method to selectively deplete host alloreactive T-cells through photodynamic therapy, using TH9402 ex vivo. The donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) is administered to the patient 28-42 days after the stem cell transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •One of the following hematological malignancies:
- •Acute Myeloid Leukemia (AML)
- •Acute Lymphoblastic Leukemia (ALL)
- •Myelodysplastic Syndrome (MDS)
- •Ph-positive chronic myeloid leukemia (CML)
- •Non-Hodgkin Lymphoma (NHL)
- •Myelodysplastic Syndrome (MDS)
- •Chronic Myeloid Leukemia (CML)
- •Multiple Myeloma (MM)
- •Chronic Lymphocytic Leukemia (CLL)
- •Myeloproliferative Syndrome (MPS)
排除标准
- •AML in 1st complete remission with good risk karyotypes
- •MM featuring concurrent extramedullar disease or being non-responsive to prior therapy
- •CML in blast crisis
- •CLL concurrently transformed into high-grade lymphoma and failing to demonstrate at least partial remission
- •NHL with concurrent bulky disease (≥ 5 cm)
- •Diffusing Capacity for Carbon Monoxide (DLCO) < 40% predicted
- •Left ventricular ejection fraction < 40%
- •AST/SGOT > 2.5 x ULN
- •Bilirubin > 1.5 x ULN
- •Creatinine > 1.5 x ULN
- •HIV positive
- •Positive pregnancy test for women of childbearing age
- •Prior haploidentical peripheral blood stem cell or cord blood transplantation
- •Less than 2 years from a prior allogeneic stem cell transplantation
- •Estimated probability of surviving less than three months
- •Major anticipated illness or organ failure incompatible with survival from transplant
- •Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and informed consent impossible
- •Known allergy to any of the components of ATIR
- •Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study
- •Donor Inclusion Criteria:
- •Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or DR loci of the unshared haplotype.
- •Male or female, age ≥ 16, ≤ 75 years.
- •Donors must be fit to receive G-CSF and undergo apheresis (normal blood count, normotensive and no history of stroke).
- •Donor must have Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
- •Donor must provide written informed consent.
- •Donor Exclusion Criteria:
- •Medically uncontrolled coronary heart disease.
- •Myocardial infarction within the last 3 months.
- •History of uncontrolled seizures.
- •History of malignancy (except basal cell or squamous carcinoma of the skin, positive PAP smear and subsequent negative follow up).
- •Positive test result for any of the mandatory viral tests in the applicable region, except for a positive cytomegalovirus (CMV) result, which does not lead to exclusion.
- •Presence of a transmissible disease (such as HIV positive), a major illness, a suspected systemic dysfunction and/or an active inflammatory or autoimmune disorder.
- •Female donors who are pregnant or nursing.
结局指标
主要结局
Transplant Related Mortality
时间窗: 6, 12 and 24 months after the transplantation
TRM is defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide)
次要结局
- Incidence and Severity Graft-versus-host Disease (GVHD)(Up to 24 months after the transplantation)
- Progression Free Survival(Up to 24 months after the transplantation)
- Incidence and Severity of Bacterial, Viral or Fungal Infection(Up to 24 months after the transplantation)
- Immune Reconstitution(Up to 24 months after the transplantation)
- Health Status (Including Quality of Life)(Up to 24 months after the transplantation)
- Overall Survival(6, 12, and 24 months after the transplantation)