Faculty Collaboration Database

A Phase II Study of Coltuximab Ravtansine (SAR3419) Monotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk 2016 Mar;16(3):139-45

Date

01/19/2016

Pubmed ID

26775883

Pubmed Central ID

PMC5557033

DOI

10.1016/j.clml.2015.12.004

Scopus ID

2-s2.0-84958922276 (requires institutional sign-in at Scopus site)   56 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/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.

Author List

Kantarjian HM, Lioure B, Kim SK, Atallah E, Leguay T, Kelly K, Marolleau JP, Escoffre-Barbe M, Thomas XG, Cortes J, Jabbour E, O'Brien S, Bories P, Oprea C, Hatteville L, Dombret H

Author

Ehab L. Atallah MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Drug Resistance, Neoplasm
Female
Humans
Immunotoxins
Male
Maytansine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Retreatment
Treatment Outcome