Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Thymoglobulin

Busulfan

Clofarabine

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Alkylating Agents

Antineoplastic Agents, Alkylating

* 30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)
* 130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)
* ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1) Corticosteroids may be used in profilaxis

* 30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)
* 130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)
* ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)

30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)

130 mg/m2/day IV busulfan once daily for 2 days (day -4 and -3)

Thymoglobuline®: 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)

30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)

Patrice CHEVALLIER, Pr

MARION GAUTIER

Patrice Chevallier, Pr

Amandine CHARBONNIER, Dr

Sylvie FRANCOIS, Dr

Ana BERCEANU, Dr

Edouard FORCADE, Dr

Gaelle GUILLERM, Dr

Sylvain CHANTEPIE, Dr

Jacques-Olivier BAY, Pr

Sebastien MAURY, Pr

Martin CARRE, Dr

Valérie COITEUX, Dr

Pascal TURLURE, Dr

Helene LABUSSIERE-WALLET, Dr

Raynier DEVILLIER, Dr

Patrice CEBALLOS, Dr

Marie-Therese RUBIO, Pr

Marie ROBIN, Dr

Stéphanie NGUYEN, Pr

Mohamad MOHTY, Pr

Natacha MAILLARD, Dr

Jean-Baptiste MEAR, Dr

Jerome CORNILLON, Dr

Anne HUYNH, Dr

patrice CHEVALLIER, Pr

Relapse remains the main cause of death in patients with myeloid malignancies, especially after an allotransplant. Using drugs with higher anti-leukemic activity as part of the conditioning regimen is one of the strategies to decrease relapse incidence in this population. Retrospective studies have shown that clofarabine can achieve impressive results compared to the use of fludarabine in acute myeloid leukemia (AML) as part of the conditioning regimen. Confirming such results in a prospective manner would definitely establish the CloB2A2 as a superior reduced-intensity conditioning (RIC) regimen compared to the FB2A2 for AML patients.302 AML patients (151 in each arm) in complete remission at transplant will be included with the main objective to demonstrate a significant better 2-year overall survival for CloB2A2 cases (70% vs 55%). A cost-utility analysis and a cost-effectiveness analysis will be also performed as well as an assessment of the quality of life after transplant. Clofarabine will be furnished to all centers. The duration of the study will be 5 years with 3 years of inclusion and 2 years of follow-up for each patient.

Study Comparing the Efficacy of 2 RIC Regimens (Clofarabine vs Fludarabine) in Adults With AML Eligible to Allo-SCT

FLUCLORIC: Randomized Multicentric Phase III Study Comparing the Efficacy of 2 Reduced Intensity Conditioning Regimens (Clofarabine/Busulfan vs Fludarabine/Busulfan) in Adults With AML and Eligible to Allogeneic Stem Cell Transplantation

OS is defined as the time from day 1 of conditioning to death or last follow-up for survivors.

* 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 day1 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 and day +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

Score of the QLQ-C30 questionnaire, including 30 questions assessing some aspects of the quality of life of cancer patients. The total score ranges from 0 to 100.

Score of the FACT-BMT questionnaire, including 50 questions assessing some aspects of the quality of life of cancer patients. The total score ranges from 0 to 200.

Graft hospitalization cost: Comparison between both groups in terms of length of stay (in days), use of antibiotics (type and length in days)

Graft hospitalization cost: Comparison between both groups in terms of blood products administered (numbers)

General Health State with Euroqol EQ-5D-5L questionnaire at Days -7, 30, 90, 180, 360 and 720; 5 answers are possible.

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 time from D1 of conditioning to death or last follow-up for survivors

Comparison of time from day1 of the conditioning to time without death or evidence of relapse or disease progression censored at the date of last follow-up.

Comparison of occurrence of veno-occlusive disease : (Mohty et al, BMT 2016) betwee

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).

Spots Global Cancer Trial Database for allogeneic stem cells transplantation