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

NCT ID: NCT07087847

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2028-09-30

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Miltenyi Biotec B.V. & Co. KG

INDUSTRY

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hu Xiaoxia

Professor of hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

Facility Contacts

Dr. Jiang, PhD, Medical Degree

Role: primary

Other Identifiers

RJ-TCD-2025

Identifier Type: -

Identifier Source: org_study_id