Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission.

Abstract : Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment × SCT interaction term. Results At 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment × SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles. Conclusion These results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission.
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01557436
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : jeudi 6 juillet 2017 - 11:29:25
Dernière modification le : jeudi 25 octobre 2018 - 01:18:03

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Xavier Thomas, Stéphane De Botton, Sylvie Chevret, Denis Caillot, Emmanuel Raffoux, et al.. Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission.. Journal of Clinical Oncology, American Society of Clinical Oncology, 2017, 35 (11), pp.1223-1230. 〈http://ascopubs.org/doi/abs/10.1200/JCO.2016.70.4551?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&〉. 〈10.1200/JCO.2016.70.4551 〉. 〈hal-01557436〉

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