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

Not Applicable

Not yet recruiting

• Conditions: Acute Leukemia; ALL (Acute B-Lymphoblastic Leukemia); Acute Leukemia Refractory; Acute Myeloid Leukemia (AML); Acute Leukemia in Relapse
• Interventions: Biological: TCRαβ+/CD45RA+depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT)

• Registration Number: NCT07087847
• Lead Sponsor: Ruijin Hospital

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-15
• Study First Submitted QC: 2025-07-24
• Last Update Submitted: 2025-07-24
• Study First Posted: 2025-07-28
• Last Update Posted: 2025-07-28
• Study Start: 2025-09-01
• Primary Completion: 2028-01-30
• Study Completion: 2028-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• 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

Exclusion Criteria

• Presence of any absolute contraindication to hematopoietic stem cell transplantation.
• Severe Comorbidities with Major Organ Dysfunction

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TCRαβ+/CD45RA+ depleted haplo-HSCT bridging with CAR-T	TCRαβ+/CD45RA+depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT)	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).

Primary Outcome Measures

Name	Time	Method
2-Year Event-Free Survival (EFS) Rate	2 years	Definition: The proportion of patients who remain free from any of the following events for 2 years post-transplantation

Trial Locations

Locations (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China