An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of Anti-minor Histocompatibility Complex (MiHA) Donor T-lymphocytes Expanded ex Vivo, in Patients With a Hematologic Malignancy, With Molecular or Clinical Relapse After Hematopoietic Stem Cell Transplantation From a Matched Donor
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Non-hematologic toxicity related to GLIDE post injection
研究概览
简要总结
This study will evaluate the safety of infusing an anti-MiHA T cell line in patients suffering from an hematologic malignancy that has relapsed following hematopoietic stem cell transplantation from a matched donor.
详细描述
The GLIDE-201/44 trial primarily aims to test the safety of anti-MiHA T cell line in patients suffering from an hematologic malignancy that has relapsed following hematopoietic stem cell transplantation from a matched donor. The anti-MiHA T cell lines are derived from the matched donor for the patient, the original donor for a given patient. Both the patient and the matched donor will undergo screening to determine the expression of targetable MiHAs. Upon identification of the target MiHAs, donor cells will be collected through apheresis and primed against the selected MiHA. In this setting, the GLIDE 201/44 product will be cryopreserved, thawed and administered as a single infusion at a target dose of 4x10E+07 viable T cells/m2 (range of dose is 0.4 4x10E+07 viable T cells/m2). A second infusion can be offered to the patients after an observation period of 42 days upon clinical evaluation by the treating physician. In the absence of secondary adverse events following the initial infusion, a second infusion of the GLIDE 201/44 product could be administered at a dose level up to 3-5 fold the original dose.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prior allogeneic HLA-matched stem cell transplantation
- •Any of the following hematologic malignancies:
- •Acute myeloid leukemia (AML)
- •Acute lymphoblastic leukemia (ALL)
- •Biphenotypic leukemia
- •Chronic lymphoblastic leukemia (CLL)
- •Hodgkin Lymphoma
- •Non-Hodgkin Lymphoma (NHL)
- •Multiple Myeloma (MM)
- •Myelodysplastic syndrome (MDS)
- •Presence of HLA2:01 and / or HLA44:02 and / or HLA-B*44:03, HLA-A*01:01; HLA-A*03:01; HLA-A*11:01;HLA A*24:02; HLA-A*29:02; HLA-A*32:01; HLA-B*07:02; HLA-B*08:01; HLA B*13:02; HLA-B*14:02; HLA-B*15:01; HLA-B*18:01; HLA-B*27:05; HLA B*35:01; HLA-B*40:01; or HLA-B*57:01
- •At least 6 months after allogeneic hematopoietic stem cell transplantation
- •Presence of detectable malignant disease post-transplantation in the form of molecular, cytogenetic or hematologic relapse of the malignant disorder.
- •Eligible to receive cytoreductive chemotherapy
- •Original stem cell donor available for leukocyte donation.
- •ECOG performance status ≤
- •Ability to provide written consent.
- •Accessible for treatment and follow up.
- •Presence of a targetable MiHA based on exome sequencing of the patient and donor
排除标准
- •Active acute GVHD > grade I
- •Prior grade III-IV acute GVHD within the last year
- •Uncontrolled chronic GVHD
- •Prior administration of donor lymphocyte infusion (DLI)
- •Use of T-cell depleting antibodies in the previous 30 days
- •Treatment with immune suppressors (oral or parenteral steroids corresponding to a dose of prednisone greater than 7.5 mg/day, calcineurine inhibitors, rapamycin, mycophenolate mofetil, etc) during the last 30 days.
- •Uncontrolled active infection
- •Uncontrolled central nervous system involvement by leukemia cells (blasts).
- •AST or ALT > 2.5 x ULN (CTCAE grade 2)
- •Bilirubin > 1.5 x ULN (CTCAE grade 2)
- •Creatinine clearance < 50 mL/min
- •Positive test for human immunodeficiency virus (HIV)
- •Positive pregnancy test (women of childbearing age only)
- •Lactating women: the safety of this therapy on breast milk is not known.
- •Estimated probability of surviving less than 3 months
- •Known allergy to any of the components of GLIDE (e.g., dimethyl sulfoxide)
- •Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.
研究组 & 干预措施
GLIDE
GLIDE single infusion at a target dose of 4x107 viable T-cells/m2
干预措施: GLIDE (Biological)
结局指标
主要结局
Non-hematologic toxicity related to GLIDE post injection
时间窗: 6 months
No death or other toxic events directly related to GLIDE injection
次要结局
- Response of hematologic malignancy (acute leukemia (ALL, AML, biphenotypic), CLL, HL, NHL, MM or MDS) post-injection(up to 12 months)
- Incidence and severity of acute and chronic graft versus host disease (GvHD)(up to 12 months)
- Persistence of GLIDE in the host and homing to peripheral blood, bone marrow and other tissues(up to 12 months)
- Non-Relapse mortality (NRM)(up to 12 months)
- Relapse-incidence (RI)(up to 12 months)
- Overall survival (OS)(up to 12 months)
- Progression-free survival (PFS)(up to 12 months)