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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

Mathilde Hunault-Berger 1 Thibaut Leguay 2 Françoise Huguet 3 Stéphane Leprêtre 4 Eric Deconinck 5, 6, 7 Mario Ojeda-Uribe Caroline Bonmati Martine Escoffre-Barbe 8 Pierre Bories 9 Chantal Himberlin Patrice Chevallier 10 Philippe Rousselot Oumedaly Reman 11 Marie-Laure Boulland 12 Séverine Lissandre 13 Pascal Turlure 14 Didier Bouscary 15, 16 Laurence Sanhes 17 Olivier Legrand 18 Marina Lafage-Pochitaloff 19 Marie C. Béné David Liens Yann Godfrin Norbert Ifrah 20, 1 Hervé Dombret 21, 22
Abstract : 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 \textless 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)
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237093
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Submitted on : Wednesday, December 2, 2015 - 4:37:44 PM
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Mathilde Hunault-Berger, Thibaut Leguay, Françoise Huguet, Stéphane Leprêtre, Eric Deconinck, et al.. 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. American Journal of Hematology, Wiley, 2015, 90 (9), pp.811--818. ⟨10.1002/ajh.24093⟩. ⟨hal-01237093⟩

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