Phase I, Dose-ranging, Open-label, Study of a Single Administration of T-cells Add-back Depleted of Host Alloreactive Cells Using Theralux™ Therapy, Following Haploidentical Peripheral Blood Stem Cell Transplantation Submitted to CD34+ Cell Selection, in Patients With Severe Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose and evaluate the safety of the administration of donor lymphocytes depleted of alloreactive T-cells following a stem cell transplant from a related, haploidentical donor, in patients with severe hematologic malignancies.
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 of 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 alloreactive T-cells (ATIR) are administered to the patient 4-6 weeks after the stem cell transplant. This method enables early immune reconstitution while preventing graft-versus-host disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any of the following hematologic malignancies: very high risk leukemia, acute leukemia, chronic myeloid leukemia (CML), lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS)
- •Incompatibility at two to three loci (HLA-A, B and/or DR) or a single DR locus of the unshared haplotype between the donor and recipient
- •Life expectancy of at least 3 months
- •Satisfactory performance status (ECOG ≤ 2);
排除标准
- •Possibility of performing an allogeneic transplant with an HLA (human leukocyte antigen) matched sibling donor
- •Availability of an 6/6 HLA-A, B and DRB1 matched unrelated donor within 2-3 months;
- •Pregnancy
- •Viral hepatitis (B or C)
- •Active serious infectious process
- •HIV positivity;
- •Systemic dysfunction (cardiac, pulmonary, hepatic and renal) contra-indicating allogeneic stem cell transplantation
- •Prior allogeneic transplantation
- •Prior autologous transplantation within twelve months of baseline visit
- •Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome
- •Active central nervous system (CNS) disease at baseline
- •Participation in a trial with an investigational agent within 30 days prior to entry in the study
- •Malignant cells in circulating peripheral blood (> 25%)
- •Other active malignant disease that would severely limit life expectancy
结局指标
主要结局
Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV
时间窗: Within 30 days after ATIR infusion
次要结局
- Occurrence of adverse drug reactions(Until 18 months after ATIR infusion)
- Rate of disease relapse(Until 60 months after ATIR infusion)
- Immune reconstitution(Until 60 months after ATIR infusion)
- Occurrence and severity of graft-versus-host disease(Until 60 months after ATIR infusion)
- Incidence and severity of infections(Until 18 months after ATIR infusion)