A Phase 2 study of L‐asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL‐SA2‐2008 study. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Hunault‐Berger, Mathilde; Leguay, Thibaut; Huguet, Françoise; Leprêtre, Stéphane; Deconinck, Eric; Ojeda-Uribe, Mario; Bonmati, Caroline; Escoffre‐Barbe, Martine; Bories, Pierre; Himberlin, Chantal; Chevallier, Patrice; Rousselot, Philippe; Reman, Oumedaly; Boulland, Marie‐Laure; Lissandre, Severine; Turlure, Pascal; Bouscary, Didier; Sanhes, Laurence; Legrand, Ollivier; Lafage‐Pochitaloff, Marina; Béné, Marie C; Liens, David; Godfrin, Yann; Ifrah, Norbert; Dombret, Hervé; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)
• Is Part Of: American journal of hematology. Volume 90:Issue 9(2015:Sep.)
• Page Start: 811
• Page End: 818
• Publication Date: 2015-09
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24093
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>Purpose</bold>: The GRASPALL/GRAALL‐SA2‐2008 Phase II trial evaluated the safety and efficacy of L‐asparaginase encapsulated within erythrocytes (GRASPA®) in patients ≥ 55 years with Philadelphia chromosome‐negative acute lymphoblastic leukemia. <bold>Findings</bold>: Thirty patients received escalating doses of GRASPA<sup>®</sup> on Day 3 and 6 of induction Phases 1 and 2. The primary efficacy endpoint was asparagine depletion < 2 µmol/L for at least 7 days. This was reached in 85 and 71% of patients with 100 and 150 IU/kg respectively but not with 50 IU/kg. Grade 3/4 infection, hypertransaminasemia, hyperbilirubinemia and deep vein thrombosis occurred in 77, 20, 7, and 7% of patients, respectively. No allergic reaction or clinical pancreatitis was observed despite 17% of Grade 3/4 lipase elevation. Anti‐asparaginase antibodies were detected in 50% of patients and related to a reduction in the duration of asparagine depletion during induction Phase 2 without decrease of encapsulated L‐asparaginase activity. Complete remission rate was 70%. With a median follow‐up of 42 months, median overall survival was 15.8 and 9.7 months, in the 100 and 150 IU/kg cohorts respectively. <bold>Conclusions</bold>: The addition of GRASPA<sup>®</sup>, especially at the 100 IU/kg dose level, is feasible in elderly patients without excessive toxicity and associated with durable asparagine depletion. (<ext-link ext-link-type="uri" xlink:href="http://clinicaltrials.gov" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">clinicaltrials.gov</ext-link> identifier NCT01523782). Am. J. Hematol. 90:811–818, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>