Prospective, Single-Center, Single-Arm Clinical Study of Ex Vivo T-Cell-Depleted Haploidentical Transplantation Bridging With Chimeric Antigen Receptor T-cell Therapy and Prophylactic Memory T Cell Infusion for Acute Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- 2-Year Event-Free Survival (EFS) Rate
研究概览
简要总结
CAR-T therapy has evolved as a pivotal treatment for relapsed/refractory (R/R) leukemia, demonstrating improved remission rates and manageable adverse events. However, over 50% of patients achieving complete remission (CR) experience relapse within one year (1-year cumulative incidence rate, CIR) due to antigen escape, CAR-T functional exhaustion, premature cell depletion, and immunosuppressive microenvironments. Novel strategies are urgently needed to sustain durable responses.
Bridging CAR-T therapy with TCRαβ+ and CD45RA+ cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) offers dual benefits: Graft-versus-leukemia (GvL) effects mediated by donor-derived NK cells and γδT cells target non-CAR-dependent antigens, mitigating immune evasion. Rapid hematopoietic reconstitution reduces prolonged cytopenia-related complications from prior therapies. This protocol further incorporates prophylactic CD45RO+ memory T-cell (Tm) infusion to: Minimize graft-versus-host disease (GVHD) risks compared to conventional donor lymphocyte infusion (DLI). Enhance adoptive immunity against infections/relapse via transferred donor memory immunity. We design this prospective, single-center, single-arm trial to evaluate the efficacy/safety of this approach using the CliniMACS® system for ex vivo TCRαβ+/CD45RA+ depletion in R/R leukemia patients post-CAR-T.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: Patients with refractory or relapsed (R/R) leukemia.
- •Donor Availability: No matched sibling or unrelated donor identified through HLA typing.
- •Disease Status Post-CAR-T: including achieved complete remission (CR), minimal residual disease (MRD)-negative in bone marrow and no extramedullary relapse.
- •Normal Organ Function (meeting the following criteria): including liver function: ALT/AST ≤10×ULN (upper limit of normal), total bilirubin (TBIL) ≤5×ULN, renal function: BUN and serum creatinine (Cr) ≤1.25×ULN and cardiac function: No evidence of cardiac insufficiency (confirmed by ECG and echocardiography).
- •Informed Consent: a signed informed consent form (ICF) is obtained
排除标准
- •Presence of any absolute contraindication to hematopoietic stem cell transplantation.
- •Severe Comorbidities with Major Organ Dysfunction
研究组 & 干预措施
TCRαβ+/CD45RA+ depleted haplo-HSCT bridging with CAR-T
For patients with refractory/relapsed (R/R) leukemia:
Approximately 28 days post-CAR-T therapy, a hematologic assessment will be performed. Eligible patients meeting the inclusion criteria will subsequently undergo TCRαβ+/CD45RA+-depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
干预措施: TCRαβ+/CD45RA+depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (Biological)
结局指标
主要结局
2-Year Event-Free Survival (EFS) Rate
时间窗: 2 years
Definition: The proportion of patients who remain free from any of the following events for 2 years post-transplantation
次要结局
未报告次要终点
研究者
Hu Xiaoxia
Professor of hematology
Ruijin Hospital