This study aims to evaluate the safety and efficacy of a Venetoclax and hypomethylating agent-based regimen combined with infusion of HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cells (GPBMC) in patients with intermediate-risk and higher myelodysplastic syndromes who are ineligible for allogeneic hematopoietic stem cell transplantation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given PO. For the first cycle, dose of 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3-14. For other cycles, dose of 400 mg on Days 1-14. Note: The dose should be reduced to 100-200 mg daily if concomitant azole antifungals are required.
AZA: Given SC. Dose of 75 mg/m² on Days 1-7 of each cycle. DAC: Given IV. Dose of 20 mg/m² on Days 1-5 of each cycle.
HLA-mismatched donor GPBMCs are infused on Day 15.
Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital
Beijing, China
RECRUITINGOverall survival (OS)
OS is defined as the number of days from the date of study entry to the date of death.
Time frame: Measured up to 4 years after the last participant is enrolled
Overall response rate (ORR)
ORR is defined as complete remission (CR) (or CR equivalent) + partial remission (PR) + CR with limited count recovery (CRL) + CR with partial hematologic recovery (CRh) + hematologic improvement (HI) according to IWG 2023 criteria.
Time frame: Measured up to 2 years after the last participant is enrolled
Modified overall response (mOR)
Modified OR is defined as CR+PR+CRL+CRh.
Time frame: Measured up to 2 years after the last participant is enrolled
Complete remission (CR)
CR is defined as absolute neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, Hb ≥10 g/dL, bone marrow with \< 5% blasts, and PB blasts 0%.
Time frame: Measured up to 2 years after the last participant is enrolled
Partial remission (PR)
PR is defined as decrease of at least 50% in the percentage of blasts still ≥5% in the bone marrow, peripheral blood neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, Hb ≥10 g/dL.
Time frame: Measured up to 2 years after the last participant is enrolled
CR with limited count recovery (CRL)
CRL is defined as bone marrow with less than 5% blasts, PB blasts 0%, and PB only meeting 1 or 2 of the following: absolute neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, Hb ≥10 g/dL.
Time frame: Measured up to 2 years after the last participant is enrolled
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CR with partial hematologic recovery (CRh)
CRh is defined as bone marrow with less than 5% blasts, and PB not meeting criteria for CR or CRL, no Hb threshold required, platelets ≥50 × 109/L, neutrophils ≥0.5 × 109/L, blasts 0%.
Time frame: Measured up to 2 years after the last participant is enrolled
Progression-free survival (PFS)
PFS is defined as the number of days from the date of study entry to the date of the first of the following events: progressed disease; relapse from CR (or CR equivalent), PR, CRL, CRh, or HI; death from any cause.
Time frame: Measured up to 4 years after the last participant is enrolled
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