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 |
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| Authors: | Mathilde Hunault‐Berger,Thibaut Leguay,Fran oise Huguet,St phane Leprê tre,Eric Deconinck,Mario Ojeda-Uribe,Caroline Bonmati,Martine Escoffre‐Barbe,Pierre Bories,Chantal Himberlin,Patrice Chevallier,Philippe Rousselot,Oumedaly Reman,Marie‐Laure Boulland,Severine Lissandre,Pascal Turlure,Didier Bouscary,Laurence Sanhes,Ollivier Legrand,Marina Lafage‐Pochitaloff,Marie C B n ,David Liens,Yann Godfrin,Norbert Ifrah,Herv Dombret |
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| Affiliation: | 1. Haematology Department of Angers, Angers, France;2. Haematology Department of Bordeaux, Bordeaux, France;3. Haematology Department of Toulouse, Toulouse, France;4. Haematology Department of Rouen, Rouen, France;5. Haematology Department of Besan?on, Besan?on, France;6. Haematology Department of Mulhouse, Mulhouse, France;7. Haematology Department of Nancy, Nancy, France;8. Haematology Department of Rennes, Rennes, France;9. Haematology Department of Strasbourg, Strasbourg, France;10. Haematology Department of Reims, Reims, France;11. Haematology Department of Nantes, Nantes, France;12. Haematology Department of Versailles, Versailles, France;13. Haematology Department of Caen, Caen, France;14. Haematology Department of Tours, Tours, France;15. Haematology Department of Limoges, Limoges, France;16. Haematology Department of Cochin APHP Paris, France;17. Haematology Department of Perpignan, Perpignan, France;18. Haematology Department of Saint Antoine APHP Paris, France;19. Genetic Department of AP‐HM Marseille, France;20. Haematology Department of ERYTECH Pharma, France;21. Haematology Department of Saint‐Louis AP‐HP Paris, France |
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| 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 < 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. |
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