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

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.

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Key information

Conditions

Acute Leukemia ALL (Acute B-Lymphoblastic Leukemia) Acute Leukemia Refractory Acute Leukemia in Relapse Acute Myeloid Leukemia (AML) Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location contact

Dr. Jiang, PhD, Medical Degree

CONTACT

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TCRαβ+/CD45RA+depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT)

Biological

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.

Primary outcomes

2-Year Event-Free Survival (EFS) Rate

Time frame: 2 years

Definition: The proportion of patients who remain free from any of the following events for 2 years post-transplantation

Sponsors and collaborators

Lead sponsor

Ruijin Hospital

Other

Collaborators

Miltenyi Biotec B.V. & Co. KG

Registry information

Official study title

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

Important dates

Study start: 2025
Primary completion: 2028
Study completion: 2028
First posted: Jul 28, 2025
Registry last updated: Jul 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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