Allogeneic γ9δ2 T Cells for the Treatment of Recurrent Hematologic Tumors After Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
This is an open single-arm clinical study aimed at evaluating the safety and tolerance of allogeneic γ9δ2 T cell injection in the treatment of patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation.
详细描述
To evaluate the safety and in vivo dynamics of allogeneic γ9δ2 T cell in the treatment of recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation patients, and to explore the appropriate therapeutic 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
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 12-65 (inclusive)；
- •Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation；
- •Basically normal liver and kidney function (as demonstrated by the following laboratory tests prior to initial γ9δ2 T cell therapy)
- •Alanine transaminase/aspartate transaminase < 2.5×ULN；
- •serum creatinine < 1.5×ULN；
- •total bilirubin level < 1.5×ULN；
- •No obvious hereditary disease;
- •Normal cardiac function, cardiac ejection index above 55%;
- •Women of reproductive age (15 to 49 years) must undergo a pregnancy test within 7 days before starting treatment and the result is negative, and use contraception during the clinical trial period and within 3 months after the last cell transfusion;
- •Sign informed consent.
排除标准
- •Patients with simple extramedullary recurrence;
- •Pregnant and lactating women;
- •Organ failure;
- •Heart: Ⅲ level and Ⅳ level;
- •Liver: reach the grade C Child - Turcotte liver function;
- •Kidney, renal failure and uremia period;
- •Lung: symptoms of severe respiratory failure;
- •Brain: consciousness disorder.
- •Patients with a history of solid organ transplantation;
- •Uncontrollable infectious diseases or other serious diseases, including but not limited to infections (such as HIV positive), congestive heart failure, unstable angina, arrhythmia, psychosis, or restricted social circumstances or those that the attending physician considers to pose unpredictable risks;
- •Patients with systemic autoimmune diseases or primary immunodeficiency;
- •Patients with allergic constitution;
- •Use of systemic steroid drugs;
- •Chronic diseases requiring the use of immunological agents or hormone herapy;
- •Prior treatment with any other immune cells;
- •Participated in similar clinical trials within 30 days;
- •Received radiation therapy within 4 weeks from the time of enrollment;
- •Researchers don't think clinical trials are appropriate for other reasons.
研究组 & 干预措施
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells
干预措施: allogeneic γ9δ2 T Cells (Biological)
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells
干预措施: Fludarabine (Drug)
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells
干预措施: Cyclophosphamide (Drug)
Patients with recurrent hematologic tumors after allogeneic hematopoietic stem cell transplantation
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, zoredronic acid depending on the patient's status, followed by investigational therapy, allogeneic γ9δ2 T Cells
干预措施: Zoredronic acid (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: 12 months
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic γ9δ2 T cells infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: First infusion date of allogeneic γ9δ2 T cells to 14 days end cell infusion
DLT was defined as allogeneic γ9δ2 T Cells-related events with onset within first 14 days following infusion: The development of Grade (G) III-IV acute GVHD according to the Mount Sinai Acute GVHD International Consortium criteria; The development of G3 or higher grade CRS lasting \> 2 weeks; Any allogeneic γ9δ2 T cells-related AE requiring intubation; All G4 non-hematologic toxicities. Symptoms of GVHD include but are not limited to skin rash, enterocolitis with diarrhea, liver dysfunction with jaundice, fever, weight loss, etc.
Maximum tolerated dose (MTD)
时间窗: 14 days
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
Recommended phase 2 dose (RP2D)
时间窗: 14 days
The recommended dose for phase 2 was determined through phase 1 study
次要结局
- Overall Survival (OS)(12 months)
- Progression Free Survival (PFS)(12 months)
- Pharmacokinetics: Persistence of the allogeneic γ9δ2 T cells(14 days)
- Pharmacodynamics: Peak level of cytokines in serum(14 days)
研究者
Xiaoyu Zhu
Director of Hematology Department
Anhui Provincial Hospital