l‐asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005‐01 randomized trial

• Published in: British journal of haematology Vol. 153; no. 1; pp. 58 - 65
• Main Authors: Domenech, Carine, Thomas, Xavier, Chabaud, Sylvie, Baruchel, Andre, Gueyffier, François, Mazingue, Françoise, Auvrignon, Anne, Corm, Selim, Dombret, Herve, Chevallier, Patrice, Galambrun, Claire, Huguet, Françoise, Legrand, Faezeh, Mechinaud, Françoise, Vey, Norbert, Philip, Irène, Liens, David, Godfrin, Yann, Rigal, Dominique, Bertrand, Yves
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2011; Blackwell; Wiley
• Subjects: Acute lymphatic leukemia; Adolescent; Adult; Antineoplastic Agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - blood; Antineoplastic Agents - therapeutic use; Asparaginase; Asparaginase - administration & dosage; Asparaginase - adverse effects; Asparaginase - blood; Asparaginase - therapeutic use; Asparagine; Biological and medical sciences; Bioreactors; Cancer; Child; Child, Preschool; childhood leukaemia; Children; Clinical trials; Coagulation; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Carriers; Drug Delivery Systems; Enzymes; Erythrocytes; Erythrocytes - enzymology; Escherichia coli; Hematologic and hematopoietic diseases; Humans; Hypersensitivity; Infant; Intravenous administration; L-asparaginase; leukaemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Life Sciences; Male; Medical sciences; Middle Aged; new drugs for leukaemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Young Adult; Human; Antineoplastic agent; Drug; Load; Relapse; Treatment resistance; Hematology; Enzyme; Red blood cell; Malignant hemopathy; Blood cell; Randomization; erythrocytes; Lymphoproliferative syndrome; childhood leukaemia; Hydrolases; Adult; Clinical trial; leukaemia; Acute lymphocytic leukemia; new drugs for leukaemia; Child; Asparaginase; Cancer
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2011.08588.x

Summary
l‐asparaginase encapsulated within erythrocytes (GRASPA®) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005‐01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA® for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA® (50 iu/kg: n = 6, 100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l‐asparaginase (E. colil‐ASNase) control group. GRASPA® was effective at depleting l‐asparagine. One single injection of 150 iu/kg of GRASPA® provided similar results to 8 × 10 000 iu/m2 intravenous injections of E. colil‐ASNase. The safety profile of GRASPA® showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil‐ASNase and there was also no difference between the three doses of GRASPA®.