International Clinical Trial Suggests Value of Venetoclax Combination Therapy in Patients with B-Cell Non-Hodgkin Lymphoma
June 6, 2016 12:51 PM
A new global multi-center study co-authored by John Theurer Cancer Center (JTCC) at Hackensack University Medical Center researchers and presented here today at the American Society of Clinical Oncology (ASCO) annual meeting concludes that venetoclax, a selective, potent oral BCL-2 inhibitor with activity in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) in combination with standard therapeutic regimens, was well-tolerated and provides evidence of its potential therapeutic value in this patient population.
The open-label, dose-finding trial, “Phase 1b study of Venetoclax Plus R- or G-CHOP in Patients with B-cell Non-Hodgkin Lymphoma,” (Abstract No. 7566, Poster no. 122) evaluated a regimen used commonly in the treatment of NHL known as CHOP (Cyclophosphamide, Hydroxydaunomycin, Oncovin, Prednisone) in combination with either rituximab or obinutuzumab, to which venetoclax was added.
“This is the first study exploring the BCL2 inhibitor venetoclax in combination with standard therapies in patients with large cell lymphoma. The result showed clinical feasibility and promising results while helping define the optimal dosing for the upcoming phase II multi-center trial,” said Andre Goy, M.D., M.S., Chairman and Director, Lymphoma Division, John Theurer Cancer Center. “Although still at an early stage targeting BCL2, which is a critical molecule controlling programmed cell death opens a completely new chapter in oncology. Venetoclax was recently approved in relapse refractory chronic lymphocytic leukemia with 17p deletion based on remarkable phase II data. This provides an opportunity to build up by combining with other regimens used in leukemia and lymphoma as in the current study.”
Previous studies in NHL xenograft models have shown that venetoclax may enhance efficacy of rituximab plus CHOP (R-CHOP), or obinutuzumab plus CHOP (G-CHOP) therapies. This study sought to assess safety and tolerability of venetoclax in combination with R-CHOP or G-CHOP in patients with no more than one previous course of therapy and to determine the maximum tolerable dose (MTD) and define appropriate dose of venetoclax for a subsequent Phase 2 study and assess optimal therapeutic benefit.
Primary outcome measures for the study are incidence of dose-limiting toxicities and complete response (CR) as defined by PET/CT scan and bone marrow examination. The expected study completion date is April 2018.
As of November 30, 2015, 46 patients were enrolled in four cohorts and divided into two arms – rituximab plus CHOP (Arm A) and obinutuzumab plus CHOP (Arm B). Patients in cohort 1 received venetoclax 200−800 mg on cycle 1, day 4, and then daily for 8 cycles. In cohorts 2-4, patients received venetoclax on cycle 1, days 4-10 and cycles 2-8, days 1-10. CHOP was administered for six 21-day cycles. Rituximab was given on day 1 of cycles 1-8 (Arm A), while obinutuzumab was given on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-8 (Arm B). The most grade common adverse events were nausea (48%), fatigue (41%), and diarrhea (41%), and the most common grade 3-4 adverse events were neutropenia (37%) and febrile neutropenia (26%).
Researchers determined that venetoclax combined with R- or G-CHOP was well-tolerated, and concluded that the appropriate dose for a Phase 2 study combining venetoclax with R-CHOP was 800mg on cycle 1, days 4-10 and cycle 2-8, days 1-10. Dose finding for venetoclax plus G-CHOP dose finding is ongoing, according to the investigators, who will present their latest findings during the ASCO meeting.
Additional information about the trial may be accessed at https://clinicaltrials.gov/show/NCT02055820.
About John Theurer Cancer Center at Hackensack University Medical Center
John Theurer Cancer Center is New Jersey’s largest and most comprehensive cancer center dedicated to the diagnosis, treatment, management, research, screenings, preventive care, as well as survivorship of patients with all types of cancer.
Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. The 14 specialized divisions feature a team of medical, research, nursing and support staff with specialized expertise that translates into more advanced, focused care for all patients. John Theurer Cancer Center provides comprehensive multidisciplinary care, state of the art technology, and access to clinical trials, compassionate care and medical expertise— all under one roof. Physicians at John Theurer Cancer Center are members of Regional Cancer Care Associates, one of the nation’s largest professional hematology/oncology groups. For more information please visit www.jtcancercenter.org.