PMID- 26775883
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20210103
IS  - 2152-2669 (Electronic)
IS  - 2152-2650 (Print)
IS  - 2152-2669 (Linking)
VI  - 16
IP  - 3
DP  - 2016 Mar
TI  - A Phase II Study of Coltuximab Ravtansine (SAR3419) Monotherapy in Patients With 
      Relapsed or Refractory Acute Lymphoblastic Leukemia.
PG  - 139-45
LID - S2152-2650(15)01431-7 [pii]
LID - 10.1016/j.clml.2015.12.004 [doi]
AB  - 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. PATIENTS AND 
      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. CONCLUSION: 
      Coltuximab ravtansine was well tolerated but was associated with a low clinical 
      response rate in patients with relapsed or refractory ALL.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Kantarjian, Hagop M
AU  - Kantarjian HM
AD  - MD Anderson Cancer Center, Houston, TX. Electronic address: 
      hkantarjian@mdanderson.org.
FAU - Lioure, Bruno
AU  - Lioure B
AD  - CHU Hautepierre, Strasbourg, France.
FAU - Kim, Stella K
AU  - Kim SK
AD  - University of Texas Health Medical School, The Robert Cizik Eye Clinic, Houston, 
      TX.
FAU - Atallah, Ehab
AU  - Atallah E
AD  - Medical College of Wisconsin, Milwaukee, WI.
FAU - Leguay, Thibaut
AU  - Leguay T
AD  - Hospital Group South, Pessac, France.
FAU - Kelly, Kevin
AU  - Kelly K
AD  - Cancer Therapy & Research Center, University of Texas Health Science Center, San 
      Antonio, TX.
FAU - Marolleau, Jean-Pierre
AU  - Marolleau JP
AD  - CHU Hospital South, Amiens, France.
FAU - Escoffre-Barbe, Martine
AU  - Escoffre-Barbe M
AD  - Hospital Pontchaillou, Rennes, France.
FAU - Thomas, Xavier G
AU  - Thomas XG
AD  - Centre Hospitalier Lyon Sud, Pierre Benite, France.
FAU - Cortes, Jorge
AU  - Cortes J
AD  - MD Anderson Cancer Center, Houston, TX.
FAU - Jabbour, Elias
AU  - Jabbour E
AD  - MD Anderson Cancer Center, Houston, TX.
FAU - O'Brien, Susan
AU  - O'Brien S
AD  - University of California, Irvine, Irvine, CA.
FAU - Bories, Pierre
AU  - Bories P
AD  - CHU Hautepierre, Strasbourg, France.
FAU - Oprea, Corina
AU  - Oprea C
AD  - Sanofi, Vitry-sur-Seine, France.
FAU - Hatteville, Laurence
AU  - Hatteville L
AD  - Sanofi, Vitry-sur-Seine, France.
FAU - Dombret, Herve
AU  - Dombret H
AD  - Hospital Saint-Louis, University Institute of Hematology, University Paris 
      Diderot, Paris, France.
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20151221
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunotoxins)
RN  - 14083FR882 (Maytansine)
RN  - MRS84YT9L2 (coltuximab ravtansine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse 
      effects/*therapeutic use
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Immunotoxins/administration & dosage/adverse effects/*therapeutic use
MH  - Male
MH  - Maytansine/administration & dosage/adverse effects/*analogs & 
      derivatives/therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/mortality/*pathology
MH  - Recurrence
MH  - Retreatment
MH  - Treatment Outcome
PMC - PMC5557033
MID - NIHMS882711
OTO - NOTNLM
OT  - Adult
OT  - Antibody-drug conjugate
OT  - CD19
OT  - Maytansine derivatives
OT  - Safety
EDAT- 2016/01/19 06:00
MHDA- 2016/12/15 06:00
PMCR- 2017/08/15
CRDT- 2016/01/19 06:00
PHST- 2015/11/18 00:00 [received]
PHST- 2015/12/14 00:00 [accepted]
PHST- 2016/01/19 06:00 [entrez]
PHST- 2016/01/19 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2017/08/15 00:00 [pmc-release]
AID - S2152-2650(15)01431-7 [pii]
AID - 10.1016/j.clml.2015.12.004 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2016 Mar;16(3):139-45. doi: 
      10.1016/j.clml.2015.12.004. Epub 2015 Dec 21.