Title: Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study
Authors: Van Den Neste, Eric ×
Cazin, Bruno
Janssens, Ann
González-Barca, Eva
Terol, María José
Levy, Vincent
Pérez de Oteyza, Jaime
Zachee, Pierre
Saunders, Andrew
de Frias, Mercè
Campàs, Clara #
Issue Date: Mar-2013
Publisher: Springer-Verlag
Series Title: Cancer chemotherapy and pharmacology vol:71 issue:3 pages:581-91
Abstract: PURPOSE: Acadesine has shown in vitro to selectively induce apoptosis in B cells from chronic lymphocytic leukemia (CLL) patients. We conducted a phase I/II open-label clinical study, to determine the safety and tolerability of acadesine given intravenously as a 4-h infusion to CLL patients. METHODS: Patient population included CLL patients with relapsed/refractory disease who had received one or more prior lines of treatment including either a fludarabine or an alkylator-based regimen. Twenty-four patients were included: eighteen in Part I treated at single doses of 50-315 mg/kg, and six in Part II, three with two doses at 210 mg/kg and three with five doses at 210 mg/kg. RESULTS: A manageable and predictable safety profile was demonstrated for acadesine at single doses between 50 and 210 mg/kg; 210 mg/kg was the maximum tolerated dose (MTD) and optimal biological dose (OBD). Grade ≥2 hyperuricemia occurred commonly but was not clinically significant and resolved with the administration of prophylactic allopurinol. Other adverse events included transient anemia and/or thrombocytopenia (not clinically significant), renal impairment, and transient infusion-related hypotension (clinically significant). Trends of efficacy such as a reduction of peripheral CLL cells and reduction in lymphadenopathy were observed; however, the results were variable due to the small population and the range of doses tested. CONCLUSIONS: A MTD of 210 mg/kg was established with single acadesine dose. Multiple dose administrations at the OBD were tested with an acceptable safety profile, showing that acadesine might be a valuable agent for the treatment of relapsed/refractory CLL patients.
ISSN: 0344-5704
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cell and Gene Therapy Applications (-)
× corresponding author
# (joint) last author

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