Phase I/II trial of nanomolecular liposomal annamycin in adult patients with relapsed/refractory acute lymphoblastic leukemia

Background: Treatment options for relapsed/refractory ALL in adult patients remain challenging. Annamycin is a highly lipophilic form of the anthracycline doxorubicin with the ability to bypass multidrug resistance mechanisms of cellular drug resistance. Patients and Methods: We performed a phase I/II multicenter, open-label, study to determine the maximally tolerated dose (MTD) of nanomolecular liposomal annamycin in adult patients with refractory ALL. Results: Thirty-one patients were enrolled; the MTD was determined to be 150 mg/m²/d for 3 days. Other than tumor lysis syndrome, there were 3 grade 3 mucositis which comprised the MTD determination. There was also 1 case each of grade 3 diarrhea, typhlitis, and nausea. After determining the MTD, a 10-patient phase IIA trial was conducted. Eight of the patients completed 1 cycle of the 3 days of treatment at the MTD. Of these, 5 (62%) had an efficacy signal with complete clearing of circulating peripheral blasts. Three of these subjects also cleared bone marrow blasts with 1 subsequently proceeding onto successful stem cell transplantation. Conclusion: Single-agent nanomolecular liposomal annamycin appears to be well tolerated, and shows evidence of clinical activity as a single agent in refractory adult ALL.