This is a Phase 1 clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of chemotherapy combining with HLA-mismatched G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusion as a bridging therapy to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed and refractory (R/R) leukemia.
Eligible patients will firstly receive chemotherapy combining with infusion of HLA-mismatched GPBMCs with the aim to reduce leukemia burden. Secondly, they will receive allo-HSCT per protocol. GPBMCs used in the first-step infusion will be derived from a sibling or unrelated donor, and GPBMCs used in the allo-HSCT procedure will be derived from an alternative donor, or the same donor (haploidentical/matched sibling/HLA 9-10 loci matched unrelated) as in the first step. The primary endpoint is the incidence of treatment-related adverse events (AEs) within 100 days post allo-HSCT, including graft-versus-host disease (GVHD), infection, organ dysfunction, and hematological toxicity. Secondary endpoints include overall survival (OS) at 1 and 2 years, progression-free survival (PFS), and graft-versus-host disease-free, relapse-free survival (GRFS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Available chemotherapy regimens include but not limited to FLAG (fludarabine, cytarabine, G-CSF), DAV (daunorubicin, cytarabine, venetoclax), IAV (idarubicin, cytarabine, venetoclax), VDCP (vincristine, daunorubicin, cyclophosphamide, prednisone), hyper-CVAD A (cyclophosphamide, vincristine, doxorubicin, dexamethasone), FC (fludarabine and cyclophosphamide), et al.
HLA-mismatched GPBMCs are infused following chemotherapy.
Patients receive conditioning including but not limited to fludarabine, cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation (TBI). HLA-matched sibling/haploidentical/unrelated GPBMCs are infused at day 0. Post-transplant cyclophosphamide, tacrolimus/cyclosporin, and mycophenolate mofetil are administered as graft-versus-host disease prophylaxis.
Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital
Beijing, China
RECRUITINGGraft-Versus-Host Disease (GVHD)
Including acute GVHD (aGVHD) and chronic GVHD (cGVHD), assessed per international universal criteria (e.g., Glucksberg classification).
Time frame: Measured up to 2 years after the last participant is enrolled
Infections
Covering bacterial, viral, fungal infections (e.g., pneumonia, sepsis, cytomegalovirus infection), confirmed based on clinical symptoms, laboratory tests, and etiological evidence.
Time frame: Measured up to 2 years after the last participant is enrolled
Hematological Toxicity
Including neutropenia, thrombocytopenia, anemia, etc., graded according to the Common Terminology Criteria for Adverse Events (CTCAE) standards.
Time frame: Measured up to 2 years after the last participant is enrolled
Progression-Free Survival (PFS)
Time from the completion of allo-HSCT to disease progression, relapse, or death from any cause.
Time frame: Measured up to 4 years after the last participant is enrolled
Graft-Versus-Host Disease-Free, Relapse-Free Survival (GRFS)
Time from the completion of allo-HSCT to the first occurrence of any of the following events: grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, disease relapse, or death.
Time frame: Measured up to 4 years after the last participant is enrolled
Overall Survival (OS)
Time from the completion of allo-HSCT to death from any cause.
Time frame: Measured up to 4 years after the last participant is enrolled
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Treatment-Related Mortality (TRM)
TRM is defined as the death related to treatment instead of disease progression.
Time frame: Measured up to 2 years after the last participant is enrolled