title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA. meir.wetzler@roswellpark.org
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Debora A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Shepard
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Ford
authors.forename: Thompson L
authors.initials: TL
authors.lastname: Heffner
authors.forename: Samir
authors.initials: S
authors.lastname: Parekh
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects; D060787:Neoplasm Grading; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin; C080315:annamycin
keywords: Clinical trial; Refractory disease; Relapsed disease