{Reference Type}: Clinical Trial, Phase I
{Title}: Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study.
{Author}: Van Den Neste E;Cazin B;Janssens A;González-Barca E;Terol MJ;Levy V;Pérez de Oteyza J;Zachee P;Saunders A;de Frias M;Campàs C;
{Journal}: Cancer Chemother Pharmacol
{Volume}: 71
{Issue}: 3
{Year}: Mar 2013
{Factor}: 3.288
{DOI}: 10.1007/s00280-012-2033-5
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.