A Phase II Study of Coltuximab Ravtansine (SAR3419) Monotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia

Hagop M. Kantarjian, Bruno Lioure, Stella K. Kim, Ehab Atallah, Thibaut Leguay, Kevin Kelly, Jean Pierre Marolleau, Martine Escoffre-Barbe, Xavier G. Thomas, Jorge Cortes, Elias Jabbour, Susan O'Brien, Pierre Bories, Corina Oprea, Laurence Hatteville, Hervé Dombret

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35 Scopus citations

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. 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/m2. 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/m2 (grade 3 peripheral motor neuropathy); therefore, 70 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)139-145
Number of pages7
JournalClinical Lymphoma, Myeloma and Leukemia
Volume16
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Adult
  • Antibody-drug conjugate
  • CD19
  • Maytansine derivatives
  • Safety

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Kantarjian, H. M., Lioure, B., Kim, S. K., Atallah, E., Leguay, T., Kelly, K., Marolleau, J. P., Escoffre-Barbe, M., Thomas, X. G., Cortes, J., Jabbour, E., O'Brien, S., Bories, P., Oprea, C., Hatteville, L., & Dombret, H. (2016). A Phase II Study of Coltuximab Ravtansine (SAR3419) Monotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia. Clinical Lymphoma, Myeloma and Leukemia, 16(3), 139-145. https://doi.org/10.1016/j.clml.2015.12.004