NCT07087847

Ex Vivo T-Cell-Depleted Haploidentical Transplantation Bridging With Chimeric Antigen Receptor T-cell Therapy and Prophylactic Memory T Cell Infusion for Acute Leukemia

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

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Ruijin Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Acute Leukemia
• Acute Leukemia Refractory
• Acute Myeloid Leukemia (AML)
• ALL (Acute B-Lymphoblastic Leukemia)
• Acute Leukemia in Relapse

Interventions

Type	Name	Description
BIOLOGICAL	TCRαβ+/CD45RA+depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT)	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).Collect peripheral blood stem cells (PBSC) from the haplo-donor.Split the graft into two fractions at a 9:1 ratio, 90% fraction: subject to TCRαβ+ T-cell depletion, 10% fraction: subject to CD45RA+ T-cell depletion. Primary graft (TCRαβ+depleted and partial CD45RA+ depleted): Freshly infused into the recipient. Residual CD45RA-depleted lymphocytes: Cryopreserved for prophylactic donor lymphocyte infusion (DLI) as needed.

Timeline

• Start date: 2025-09-01
• Primary completion: 2028-01-30
• Completion: 2028-09-30
• First posted: 2025-07-28
• Last updated: 2025-07-28

Locations

1 site across 1 country: China