TY - JOUR
T1 - Phase I/II trial of nanomolecular liposomal annamycin in adult patients with relapsed/refractory acute lymphoblastic leukemia
AU - Wetzler, Meir
AU - Thomas, Debora A.
AU - Wang, Eunice S.
AU - Shepard, Robert
AU - Ford, Laurie A.
AU - Heffner, Thompson L.
AU - Parekh, Samir
AU - Andreeff, Michael
AU - O'Brien, Susan
AU - Kantarjian, Hagop M.
N1 - Funding Information:
Supported partially by grants from the National Cancer Institute Grant CA16056 (MW, ESW, LAF), the Szefel Foundation , Roswell Park Cancer Institute (ESW), the Nancy C. Cully Endowment for Leukemia Research (MW), and the Leonard S. LuVullo Endowment for Leukemia Research (MW). All authors also received funding from Callisto Pharmaceuticals (New York, NY).
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Clinical trial
KW - Refractory disease
KW - Relapsed disease
UR - http://www.scopus.com/inward/record.url?scp=84880712014&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2013.03.015
DO - 10.1016/j.clml.2013.03.015
M3 - Article
C2 - 23763920
AN - SCOPUS:84880712014
SN - 2152-2650
VL - 13
SP - 430
EP - 434
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -