Trials in progress: Phase IB/II of CPX-351 as maintenance therapy in AML patients ineligible for bone marrow transplantation

Abstract Acute myeloid leukemia (AML) patients have a high risk of relapse. In patients ineligible for allogenic hematopoietic stem cell transplant (HSCT), oral azacitidine is the only FDA approved treatment option. CPX-351 is a drug with a liposomal formulation of cytarabine and daunorubicin. The drug is currently approved as Vyxeos® for newly diagnosed therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). CPX-351 has a long half-life and has been shown to have preferential cytotoxic effects on leukemia. We hypothesize that at lower doses, CPX-351 may be beneficial maintenance treatment in patients with newly diagnosed AML in remission. This is a Phase I/II study evaluating the RP2D and the safety/tolerability of newly diagnosed AML patients who have obtained complete remission (CR) after induction treatment and are not eligible for HSCT. Eligible patients are newly diagnosed with AML in CR that have received any induction regimen with standard consolidation or a hypomethylating agent (HMA) and venetoclax, for at least 6 cycles and no more than 12 cycles. Patients must be able to start therapy within 3 months of the last documented CR and are ineligible for allogeneic HSCT (for any reason including poor performance status, patient's preference, favorable AML, or comorbidities and age precluding transplant). Prior HSCT patients are excluded, as well as cumulative lifetime anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal radiation therapy, anthracycline dose equal to or greater than 295 mg/m2. Patients will be treated with low dose CPX-351 (combination of daunorubicin 8.8mg/m2 + cytarabine 20mg/m2) on D1 and D3 of a 28-day cycle. This low dose was chosen based on prior regimens to mimic doses used with low dose cytarabine (LDAC) to minimize toxicity. Bone marrow biopsies are performed at baseline, after cycle 1, 3, 6, and then every 3 months if MRD positive. The focus of the correlative science portion of this study is to identify the presence of minimal residual disease (MRD), via flow cytometry and NGS each marrow timepoint. The study is evaluating health quality of life outcomes using a geriatric assessment, frailty score, patient reported outcomes measures and albumin at baseline and at the end of each cycle. Patients will be enrolled in a 3+3 design de-escalation design. Once the maximum tolerated dose is determined, there will be up to 20 patients enrolled in the phase II study for a total of up to 24 patients. The sample size calculation was based on the level of precision of the estimated SAE based on the binomial exact 95% confidence intervals incidences. The study is open and enrolling. Study sites include Medstar Georgetown University Hospital, Hackensack Meridan Health, and University of Pennsylvania. NCT # 04990102. As of August 1, 2025, 9 patients have been enrolled. This investigator-sponsored study was supported by a research grant and provision of study drug from Jazz Pharmaceuticals. The study was independently designed and conducted by the investigators.