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

Abstract

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/m(2)/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.

• 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
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 13 Issue 4 Pg. 430-4 (Aug 2013) ISSN: 2152-2669 [Electronic] United States
• PMID: 23763920 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Liposomes
• Doxorubicin
• annamycin

Topics

• Adult
• Aged
• Antibiotics, Antineoplastic (administration & dosage, adverse effects)
• Doxorubicin (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Humans
• Liposomes (administration & dosage, adverse effects)
• Male
• Middle Aged
• Nanoparticles (administration & dosage, adverse effects)
• Neoplasm Grading
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Recurrence
• Young Adult