title: 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.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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).
authors.affiliation: Haematology Department of Angers, Angers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Hunault-Berger
authors.affiliation: Haematology Department of Bordeaux, Bordeaux, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leguay
authors.affiliation: Haematology Department of Toulouse, Toulouse, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Huguet
authors.affiliation: Haematology Department of Rouen, Rouen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Leprêtre
authors.affiliation: Haematology Department of Besançon, Besançon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Deconinck
authors.affiliation: Haematology Department of Mulhouse, Mulhouse, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Ojeda-Uribe
authors.affiliation: Haematology Department of Nancy, Nancy, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonmati
authors.affiliation: Haematology Department of Rennes, Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Escoffre-Barbe
authors.affiliation: Haematology Department of Strasbourg, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bories
authors.affiliation: Haematology Department of Reims, Reims, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Himberlin
authors.affiliation: Haematology Department of Nantes, Nantes, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Haematology Department of Versailles, Versailles, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.affiliation: Haematology Department of Caen, Caen, France.
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.affiliation: Haematology Department of Rennes, Rennes, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Boulland
authors.affiliation: Haematology Department of Tours, Tours, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Lissandre
authors.affiliation: Haematology Department of Limoges, Limoges, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Turlure
authors.affiliation: Haematology Department of Cochin APHP Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Bouscary
authors.affiliation: Haematology Department of Perpignan, Perpignan, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Sanhes
authors.affiliation: Haematology Department of Saint Antoine APHP Paris, France.
authors.forename: Ollivier
authors.initials: O
authors.lastname: Legrand
authors.affiliation: Genetic Department of AP-HM Marseille, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Lafage-Pochitaloff
authors.affiliation: Haematology Department of Nantes, Nantes, France.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
authors.affiliation: Haematology Department of ERYTECH Pharma, France.
authors.forename: David
authors.initials: D
authors.lastname: Liens
authors.affiliation: Haematology Department of ERYTECH Pharma, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Godfrin
authors.affiliation: Haematology Department of Angers, Angers, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.affiliation: Haematology Department of Saint-Louis AP-HP Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000935:Antifungal Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001215:Asparaginase / Q000627:therapeutic use*; D001216:Asparagine / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004337:Drug Carriers; D001216:Asparagine; D001215:Asparaginase