Hagop M Kantarjian1, Bruno Lioure2, Stella K Kim3, Ehab Atallah4, Thibaut Leguay5, Kevin Kelly6, Jean-Pierre Marolleau7, Martine Escoffre-Barbe8, Xavier G Thomas9, Jorge Cortes10, Elias Jabbour10, Susan O'Brien11, Pierre Bories2, Corina Oprea12, Laurence Hatteville12, Hervé Dombret13. 1. MD Anderson Cancer Center, Houston, TX. Electronic address: hkantarjian@mdanderson.org. 2. CHU Hautepierre, Strasbourg, France. 3. University of Texas Health Medical School, The Robert Cizik Eye Clinic, Houston, TX. 4. Medical College of Wisconsin, Milwaukee, WI. 5. Hospital Group South, Pessac, France. 6. Cancer Therapy & Research Center, University of Texas Health Science Center, San Antonio, TX. 7. CHU Hospital South, Amiens, France. 8. Hospital Pontchaillou, Rennes, France. 9. Centre Hospitalier Lyon Sud, Pierre Benite, France. 10. MD Anderson Cancer Center, Houston, TX. 11. University of California, Irvine, Irvine, CA. 12. Sanofi, Vitry-sur-Seine, France. 13. Hospital Saint-Louis, University Institute of Hematology, University Paris Diderot, Paris, France.
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.
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.
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