title: Phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for allogeneic hematopoietic cell transplantation.
abstract: We conducted a phase I-II study of transplantation conditioning with clofarabine-melphalan-alemtuzumab for patients with advanced hematologic malignancies. Ten patients were accrued to the phase I portion, which utilized an accelerated titration design. No dose-limiting toxicity was observed, and clofarabine 40 mg/m(2) × 5, melphalan 140 mg/m(2) × 1, and alemtuzumab 20 mg × 5 was adopted for the phase II study, which accrued 72 patients. Median age was 54 years. There were 44 patients with acute myelogenous leukemia or myelodysplastic syndromes, 27 with non-Hodgkin lymphoma, and nine patients with other hematologic malignancies. The largest subgroup of 35 patients had American Society for Blood and Marrow Transplantation high-risk, active disease. All evaluable patients engrafted with a median time to neutrophil and platelet recovery of 10 and 18 days, respectively. The cumulative incidence of treatment-related mortality was 26% at 1 year. Cumulative incidence of relapse was 29% at 1 year. Overall survival was 80% (95% confidence interval [CI], 71-89) at 100 days and 59% (95% CI, 47-71) at 1 year. Progression-free-survival was 45% (95% CI, 33-67) at 1 year. Rapid-onset renal failure was the main toxicity in the phase II study and more frequent in older patients and those with baseline decrease in glomerular filtration rate. Grade 3-5 renal toxicity was observed in 16 of 74 patients (21%) treated at the phase II doses. Clofarabine-melphalan-alemtuzumab conditioning yields promising response and duration of response, but renal toxicity poses a considerable risk particularly in older patients.
authors.affiliation: Section of Hematology/Oncology, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. kvbesien@uchicago.edu
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rich
authors.forename: Olatoyosi
authors.initials: O
authors.lastname: Odenike
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
authors.forename: Peter H
authors.initials: PH
authors.lastname: O'Donnell
authors.forename: Justin
authors.initials: J
authors.lastname: Kline
authors.forename: Vu
authors.initials: V
authors.lastname: Nguyen
authors.forename: Paula
authors.initials: P
authors.lastname: Del Cerro
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Artz
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D000227:Adenine Nucleotides / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000367:Age Factors; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D000077866:Clofarabine; D005260:Female; D005919:Glomerular Filtration Rate; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000401:mortality / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012008:Recurrence; D012306:Risk; D016019:Survival Analysis; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000227:Adenine Nucleotides; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000074323:Alemtuzumab; D000077866:Clofarabine; D008558:Melphalan
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