title: (90)Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study.
abstract: BACKGROUND
  Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study.
  
  
  METHODS
  Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of (90)Y-DOTA-epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m(2) (92·5 MBq/m(2); level 1), 5·0 mCi/m(2) (185 MBq/m(2); level 2), 7·5 mCi/m(2) (277·5 MBq/m(2); level 3), and 10·0 mCi/m(2) (370 MBq/m(2); level 4). The primary objective was to identify the maximum tolerated dose of (90)Y-DOTA-epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457.
  
  
  RESULTS
  Between Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27-77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3-4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4).
  
  
  CONCLUSIONS
  (90)Y-DOTA-epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m(2) 1 week apart per cycle for phase 2 studies.
  
  
  BACKGROUND
  Immunomedics and Direction de la Recherche Clinique of Nantes.
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Hotel-Dieu, Nantes, France. Electronic address: patrice.chevallier@chu-nantes.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Nuclear Medicine Department, Centre Hospitalo-Universitaire, Nantes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eugene
authors.affiliation: Hematology and Biology Department, Centre Hospitalo-Universitaire, Nantes, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Robillard
authors.affiliation: Hematology Department, University Hospital, St Antoine, APHP, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Isnard
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Lyon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Nicolini
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Escoffre-Barbe
authors.affiliation: Hematology Department, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Huguet
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Angers, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Hunault
authors.affiliation: Hematology Department, Hopital Necker, Assistance-Publique Hôpitaux de Paris, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Marcais
authors.affiliation: Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Gaschet
authors.affiliation: Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France; Nuclear Medicine Department, Institut de Cancérologie de l'Ouest-Gauducheau, saint-Herblain, France; GIP ARRONAX, Saint-Herblain, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cherel
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Hotel-Dieu, Nantes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaume
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Hotel-Dieu, Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Delaunay
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Hotel-Dieu, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Peterlin
authors.affiliation: Hematology and Biology Department, Centre Hospitalo-Universitaire, Nantes, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Eveillard
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Lyon, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Angers, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.affiliation: Hematology Department, University Hospital, St Antoine, APHP, Paris, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Lapusan
authors.affiliation: Nuclear Medicine Department, Centre Hospitalo-Universitaire, Nantes, France; Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bodet-Milin
authors.affiliation: Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France; GIP ARRONAX, Saint-Herblain, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbet
authors.affiliation: Nuclear Medicine Department, Centre Hospitalo-Universitaire, Nantes, France; Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.affiliation: Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Medical Physics Department, Institut de Cancérologie de l'Ouest-Gauducheau, saint-Herblain, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Ferrer
authors.affiliation: Hematology and Biology Department, Centre Hospitalo-Universitaire, Nantes, France.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Bene
authors.affiliation: Hematology Department, Centre Hospitalo-Universitaire, Hotel-Dieu, Nantes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Le Houerou
authors.affiliation: Immunomedics, Morris Plains, NJ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Immunomedics, Morris Plains, NJ, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.affiliation: Nuclear Medicine Department, Centre Hospitalo-Universitaire, Nantes, France; Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France; Nuclear Medicine Department, Institut de Cancérologie de l'Ouest-Gauducheau, saint-Herblain, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodéré
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000532:radiotherapy*; D011446:Prospective Studies; D016499:Radioimmunotherapy; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D051918:Sialic Acid Binding Ig-like Lectin 2; D015021:Yttrium Radioisotopes; C448700:epratuzumab