title: A Phase II Study of Coltuximab Ravtansine (SAR3419) Monotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia.
abstract: BACKGROUND
  Long-term disease-free survival in adult patients with acute lymphoblastic leukemia (ALL) remains unsatisfactory, and the treatment options are limited for those patients with relapse or a failure to respond after initial therapy. We conducted a dose-escalation/expansion phase II, multicenter, single-arm study to determine the optimal dose of coltuximab ravtansine (SAR3419), an anti-CD19 antibody-drug conjugate, in this setting.
  
  
  METHODS
  The dose-escalation part of the study determined the selected dose of coltuximab ravtansine for the evaluation of efficacy and safety in the dose-expansion phase. Patients received coltuximab ravtansine induction therapy (≤ 8 weekly doses). The responding patients were eligible for maintenance therapy (biweekly administration for ≤ 24 weeks). Three dose levels of coltuximab ravtansine were examined: 55, 70, and 90 mg/m(2). The primary endpoint was the objective response rate (ORR). The secondary endpoints included the duration of response (DOR) and safety.
  
  
  RESULTS
  A total of 36 patients were treated: 19 during dose escalation and 17 during dose expansion. One dose-limiting toxicity was observed at 90 mg/m(2) (grade 3 peripheral motor neuropathy); therefore, 70 mg/m(2) was selected for the dose-expansion phase. Five patients discontinued therapy because of adverse events (AEs). The most common AEs were pyrexia, diarrhea, and nausea. Of the 17 evaluable patients treated at the selected dose, 4 had a disease response (estimated ORR using the Bayesian method: 25.5% (80% confidence interval, 14.2%-39.6%). The DOR was 1.9 months (range, 1-5.6 months). Because of these results, the study was prematurely discontinued.
  
  
  CONCLUSIONS
  Coltuximab ravtansine was well tolerated but was associated with a low clinical response rate in patients with relapsed or refractory ALL.
authors.affiliation: MD Anderson Cancer Center, Houston, TX. Electronic address: hkantarjian@mdanderson.org.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: CHU Hautepierre, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.affiliation: University of Texas Health Medical School, The Robert Cizik Eye Clinic, Houston, TX.
authors.forename: Stella K
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Ehab
authors.initials: E
authors.lastname: Atallah
authors.affiliation: Hospital Group South, Pessac, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Leguay
authors.affiliation: Cancer Therapy & Research Center, University of Texas Health Science Center, San Antonio, TX.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kelly
authors.affiliation: CHU Hospital South, Amiens, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.affiliation: Hospital Pontchaillou, Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Escoffre-Barbe
authors.affiliation: Centre Hospitalier Lyon Sud, Pierre Benite, France.
authors.forename: Xavier G
authors.initials: XG
authors.lastname: Thomas
authors.affiliation: MD Anderson Cancer Center, Houston, TX.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: MD Anderson Cancer Center, Houston, TX.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: University of California, Irvine, Irvine, CA.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: CHU Hautepierre, Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bories
authors.affiliation: Sanofi, Vitry-sur-Seine, France.
authors.forename: Corina
authors.initials: C
authors.lastname: Oprea
authors.affiliation: Sanofi, Vitry-sur-Seine, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Hatteville
authors.affiliation: Hospital Saint-Louis, University Institute of Hematology, University Paris Diderot, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008453:Maytansine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000922:Immunotoxins; D008453:Maytansine; C569646:coltuximab ravtansine
keywords: Adult; Antibody-drug conjugate; CD19; Maytansine derivatives; Safety