FLUCLORIC - Randomized multicentric Phase III study comparing the efficacy of two reduced intensity conditioning regimens (clofarabine/busulfan versus fludarabine/busulfan) in adults with acute myeloid leukemia and eligible to allogeneic stem cell transplantation: a SFGM-TC study

简要总结

主要结局

次要结局

• -Engraftment: PNN >500/mm3 + donor chimerism >=5% (day +30/42) -Primary and secondary graft failure: donor chimerism <5% at day +30/42 post-transplant (primary) or at distance of transplant after achieving engraftment (secondary)
• -Neutrophils recovery: the first of three consecutive days with neutrophils ≥500/mm3 after aplasia from day 0 of the graft -Platelets recovery: the first of three consecutive days with platelets ≥20000/mm3 without transfusion after aplasia from day 0 of the graft
• DFS: time from day 1 of the conditioning to time without death or evidence of relapse or disease progression censored at the date of last follow-up.
• Relapse: any event related to progression or re-occurrence of the disease from day 1 of the conditioning
• NRM: death from any cause without previous relapse or progression from day 1 of the conditioning
• Acute GVHD: NIH criteria
• Chronic GVHD: NIH criteria
• GRFS: alive with no previous grade III-IV acute GvHD, no moderate or severe chronic GvHD and no relapse from day 1 of the conditioning
• Chimerism: peripheral blood and CD3 T cells by molecular markers at days +30, +60, +90/100
• Immune reconstitution: Immunophenotype of PB lymphocytes and EPP: CD4, CD8, B, NK, EPP at 3, 6, 9 and 12 months
• Minimal residual disease (MRD): before transplant, at day +30/60 and dayd+90/100 by flow cytometry, molecular biology and NGS (if available) (ELN 2022 recommendation, Dohner et al Blood 2022)
• Comparison of infections after FB2A2 vs CloB2A2: bacterial, viral, parasitic and fungal between day 0 and day+90/100
• Quality of life: EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) and FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant). at D-7, D30, D90, D180 and D360
• Graft hospitalization: Comparison between both groups in terms of length of stay (in days), use of antibiotics (type and length in days) and blood products (numbers)
• General Health State with Euroqol EQ-5D-5L questionnaire at D-7, D30, D90, D180, D360 and D720.
• Health Economic study: Incremental cost-utility ratio (ICUR, cost per quality-adjusted life year [QALY] gained) and incremental cost-effectiveness ratio (ICER, cost per life year gained), from a collective perspective and with a 24-month time horizon
• Comparison of outcomes betwwen patients in first vs second line therapy and impact of clofarabine vs fludaribine in each sub-group: OS, DFS, RI, NRM
• Comparison of outcomes between patients receiving a first vs a second allograft and impact of clofarabine vs fludarabine in each sub-group: OS, DFS, RI, NRM
• dosage of leukemics blasts at diagnosis or at relapse and description of immune sub-population reconstitution post allograft (at inclusion, months 3, 6, 9 and 12).
• Comparison of occurrence of veno-occlusive disease : (Mohty et al, BMT 2016) between day 0 and day+90/100
• Safety assessment: the safety assessment shall be done by collecting all adverse events that occur during the research. All adverse event (except GvHD) shall be graded according to CTC-AE Toxicity Grading Scale (version 5).