Acute Leukemia, Acute Leukemia in Relapse, Acute Leukemia Refractory, Acute Myeloid Leukemia (AML), ALL (Acute B-Lymphoblastic Leukemia)
Conditions
Keywords
ex vivo t cell depletion, TCRab depletion, CD45RA depletion, memory T cell
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.
Interventions
BIOLOGICALTCRαβ+/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.
Sponsors
Miltenyi Biotec B.V. & Co. KG
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open, single-arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
China
Outcome results
None listed