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A P hase 2 study of L ‐asparaginase encapsulated in erythrocytes in elderly patients with P hiladelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL‐SA 2‐2008 study
Author(s) -
HunaultBerger Mathilde,
Leguay Thibaut,
Huguet Françoise,
Leprêtre Stéphane,
Deconinck Eric,
Ojeda-Uribe Mario,
Bonmati Caroline,
EscoffreBarbe Martine,
Bories Pierre,
Himberlin Chantal,
Chevallier Patrice,
Rousselot Philippe,
Reman Oumedaly,
Boulland MarieLaure,
Lissandre Severine,
Turlure Pascal,
Bouscary Didier,
Sanhes Laurence,
Legrand Ollivier,
LafagePochitaloff Marina,
Béné Marie C,
Liens David,
Godfrin Yann,
Ifrah Norbert,
Dombret Hervé
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24093
Subject(s) - asparaginase , medicine , gastroenterology , acute lymphocytic leukemia , acute pancreatitis , toxicity , deep vein , leukemia , thrombosis , lymphoblastic leukemia
Purpose : 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. Findings : Thirty patients received escalating doses of GRASPA ® 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. Conclusions : The addition of GRASPA ® , especially at the 100 IU/kg dose level, is feasible in elderly patients without excessive toxicity and associated with durable asparagine depletion. ( clinicaltrials.gov identifier NCT01523782). Am. J. Hematol. 90:811–818, 2015. © 2015 Wiley Periodicals, Inc.