Phase I/II Trial of Nanomolecular Liposomal Annamycin in Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia |
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| Authors: | Meir Wetzler Debora A. Thomas Eunice S. Wang Robert Shepard Laurie A. Ford Thompson L. Heffner Samir Parekh Michael Andreeff Susan O'Brien Hagop M. Kantarjian |
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| Affiliation: | 1. Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY;2. Leukemia Department, MD Anderson Cancer Center, Houston, TX;3. Callisto Pharmaceuticals, New York, NY;4. The Winship Cancer Institute of Emory University, Atlanta, GA;5. Albert Einstein College of Medicine, Bronx, NY;1. Danish Cancer Society Research Center, Copenhagen, DK 2100, Denmark;2. Pediatrics and Adolescence Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark;3. Institute for Clinical Medicine, University of Copenhagen, Denmark;1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India;2. Department of Biological Science, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India;1. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL;2. Division of Medical Oncology, Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY;3. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY;4. Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL |
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| Abstract: | BackgroundTreatment 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 MethodsWe 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.ResultsThirty-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.ConclusionSingle-agent nanomolecular liposomal annamycin appears to be well tolerated, and shows evidence of clinical activity as a single agent in refractory adult ALL. |
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