Phase I study of mitoxantrone hydrochloride liposome in relapsed and refractory pediatric tumors.

10049 Background: Compared with solvent-based mitoxantrone, mitoxantrone hydrochloride liposome has been found to reduce bone marrow toxicity. This open-label, single-arm phase I clinical trial was designed to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome monotherapy in the treatment of pediatric tumors. Methods: To explore the maximum tolerated dose (MTD) of mitoxantrone liposome in pediatric cancer patients, using a "3+3" design, patients received three dose levels (16mg/m 2 , 20mg/m 2 , 24mg/m 2 , d1) of mitoxantrone hydrochloride liposome monotherapy every 3 weeks. Patients were observed for dose-limiting toxicity (DLT) during the first cycle. The primary endpoint was MTD, and the secondary endpoints included objective response rate (ORR) and disease control rate (DCR), DLT, adverse events (AE), etc. Results: From October 2022 to September 2023, total of 7 pediatric cancer patients were enrolled and completed treatment, of which 6 patients received 16mg/m 2 and 1 patient received 20mg/m 2 mitoxantrone liposome monotherapy. The median age of the patients was 13.0 years (range: 8.0, 17.0). The tumor types included soft tissue sarcoma, hepatoblastoma, T-cell lymphoma, etc. The median number of treatment cycles was 2.0 (range: 1.0, 6.0). 1 patient (16mg/m 2 dose group) developed DLT, which was a grade 3 febrile neutropenia lasting more than 7 days after G-CSF. All patients could be evaluated for toxicity, and 5 patients could be evaluated for efficacy based on imaging findings. The AE of all grades with high incidence (≥50%) were white blood cell decreased (85.7%), anemia (71.4%), neutrophil count decreased (71.4%), platelet count decreased (57.1%), and anorexia (57.1%), respectively. The overall safety was acceptable. Six patients (85.7%) discontinued treatment early, of which 3 (42.9%) were due to disease progression confirmed by imaging, and 3 (42.9%) were due to limited efficacy considered by the investigators. The overall ORR and DCR were 20% (95%CI: 0.5%-71.6%) and 40% (95%CI :5.3%-85.3%), respectively. After the observation of 7 patients, the investigators thought that the efficacy of mitoxantrone liposome monotherapy was not as expected, and the study protocol was revised to continue the study of mitoxantrone liposome combined therapy. Conclusions: Mitoxantrone liposome has an acceptable safety profile in pediatric cancer patients, but the preliminary efficacy is not up to expectations, and further studies on combination therapy are needed. Clinical trial information: NCT05620862 .