Cladribine, idarubicin, and cytarabine (CLIA) for patients with relapsed and/or refractory acute myeloid leukemia: A single‐center, single‐arm, phase 2 trial

Abstract Background The treatment of relapsed and/or refractory (R/R) acute myeloid leukemia (AML) remains challenging because of poor responses to chemotherapy. Efforts to improve outcomes have included the use of high‐dose cytarabine in combination with nucleoside analogs, such as cladribine. The authors evaluated combined cladribine, idarubicin, and cytarabine (CLIA) in a phase 2 trial of 66 patients with R/R AML. Methods Patients received induction with cladribine 5 mg/m 2 intravenously (days 1–5), cytarabine 1000 mg/m 2 intravenously (days 1–5), and idarubicin 10 mg/m 2 intravenously (days 1–3; CLIA). Sorafenib 400 mg twice daily (days 1–14) was added for FLT3 ‐mutated AML. Results The composite response rate (complete remission [CR] plus complete remission with incomplete hematologic recovery [CRi]) was 33%; salvage 1 (S1) patients ( n = 35) had a CR/CRi rate of 49%. After a 61‐month median follow‐up, the median overall survival (OS) was 7.9 months, with a median relapse‐free survival (RFS) of 9.1 months for those in CR/CRi. The median OS for S1 patients was 12 months, with a median RFS of 10.3 months. For those who received CLIA with sorafenib ( n = 22), the CR/CRi rate was 41%, median OS was 8.8 months, and median RFS was 3.8 months. Landmark analysis demonstrated superior OS for patients who proceeded to transplantation compared with patients who did not (median OS, 78 vs. 8.8 months, respectively; p < .001). The 4‐week and 8‐week mortality rates were 6% and 17%, respectively. Most grade >3 adverse events were related to infection and elevated liver function tests. Conclusions CLIA is effective for patients with R/R AML and offers a safety profile similar to that of other intensive regimens (ClinicalTrials.gov identifier NCT02115295).