Weill Cornell Medical College, New York, NY
John Leonard , Pier Luigi Zinzani , Wojciech Jurczak , Mathias J. Rummel , Gilles A. Salles , Eva Kimby , Hendrik-Tobias Arkenau , Andrew John Davies , David Michael Johnson , Shelley Evans , Roger D. Dansey , Wayne R. Godfrey , Brad S. Kahl
Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, targeted, highly selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues (Lannutti et al, 2011). Phase 1 trials demonstrated that idelalisib is highly active in pts with heavily pretreated iNHL: pts experienced reductions in disease-associated chemokines, profound and rapid reductions in lymphadenopathy, and durable clinical benefit with acceptable safety profile (de Vos et al, 2011). Methods: 375 pts with previously treated iNHL, who have measurable lymphadenopathy, have received prior anti-CD20-antibody-containing therapy, and who have iNHL that is not refractory to rituximab (R) are randomized in a 2:1 ratio into Arm A or Arm B. In Arm A, pts receive idelalisib at 150 mg BID continuously + R at 375 mg/m2 (weekly x 4 then every 8 weeks x 4). In Arm B, pts receive placebo BID instead of idelalisib. Stratification factors include tumor type (follicular lymphoma vs others), tumor burden (high vs low), and time since completion of last prior therapy for iNHL (<18 months vs ≥18 months). The primary endpoint is PFS and key secondary endpoints include ORR, lymph node response rate, CR rate, and OS. This is an event-driven trial and primary endpoint evaluation will be based on independent central review. For the primary efficacy analysis, the difference in PFS between the treatment arms will be assessed in the ITT analysis set using Kaplan-Meier methods and the stratified log-rank test. The study opened for enrollment in Dec 2012 (NCT01732913). Clinical trial information: NCT01732913.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Disclosures
2014 ASCO Annual Meeting
First Author: Myron Stefan Czuczman
2013 ASCO Annual Meeting
First Author: Sven De Vos
2023 ASCO Annual Meeting
First Author: Federico Cappuzzo
2023 ASCO Annual Meeting
First Author: Jason Westin