Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study

作者：Van Den Neste Eric^*; Cazin Bruno; Janssens Ann; Gonzalez Barca Eva; Jose Terol Maria; Levy Vincent; Perez de Oteyza Jaime; Zachee Pierre; Saunders Andrew; de Frias Merce; Campas Clara

来源：Cancer Chemotherapy and Pharmacology, 2013, 71(3): 581-591.

DOI：10.1007/s00280-012-2033-5

• Acadesine
• Relapsed-refractory CLL
• Apoptosis
• Phase I/III trials
• Leukemias and lymphomas

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. %26lt;br%26gt;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. %26lt;br%26gt;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 a parts per thousand yen2 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. %26lt;br%26gt;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.

• 出版日期2013-3