A phase II study of CPX-351 in younger patients < 60 years old with secondary acute myeloid leukemia: Trial in progress.

Abstract

TPS7073 Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) and therapy-related AML (t-AML) have poor long-term outcomes following standard induction 7+3 chemotherapy. CPX-351, a liposomal formulation of cytarabine and daunorubicin fixed at the synergistic ratio of 5:1, is indicated for the treatment of pts with newly diagnosed s-AML and t-AML based on the results of a phase III trial favorably comparing CPX-351 to 7+3. Although the trial only enrolled pts aged 60-75 years (Y), CPX-351 is approved by the United States Food and Drug Administration for all adult pts with t-AML and AML with myelodysplasia-related changes (AML-MRC). In a prior retrospective analysis of CPX-351 in pts <60 Y with s-AML, we noted that the outcomes of these younger pts appeared inferior to those reported in older pts (60-75 Y) in the phase III trial (Przespolewski et al. Blood 2018 p.2677). Therefore, we designed this prospective study to evaluate the efficacy of CPX-351 in pts <60 Y with untreated s-AML and t-AML. Methods: In this phase II single-arm multi-institutional study, pts aged 18-59 Y with untreated t-AML or AML-MRC, adequate organ function, and ECOG performance status ≤ 2 are eligible. Pts with active central nervous system disease and infections were excluded. CPX-351 will be dosed at 100 mg/m2 cytarabine and 44 mg/m2 daunorubicin on days 1, 3, and 5 during induction. Bone marrow biopsy will be performed between days 14-21 to assess response. If needed, re-induction CPX-351 dose will be 44 mg/m2 daunorubicin/100 mg/m2 cytarabine on days 1 and 3. Pts achieving a complete remission (CR) following induction can receive up to 2 cycles of consolidation CPX-351 dosed as cytarabine 65 mg/m2 and daunorubicin 29 mg/m2 on days 1 and 3. The primary endpoint of the study is overall response rates defined as CR and CR with incomplete blood count recovery (CRi)) within 45 days of beginning therapy. Secondary endpoints are duration of response, event-free survival, overall survival, rate of allogeneic stem cell transplant, and adverse events. A maximum of 46 pts will be enrolled at 4 U.S. sites with 5-year follow-up from the start of CPX-351.The study is open and has enrolled 4 pts to date. Clinical trial information: NCT04269213.