NCT02055820

A Study Evaluating the Safety, Efficacy and Pharmacokinetics of Venetoclax Combined With Chemotherapy in Participants With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL

A Phase Ib/II, Open-Label Study Evaluating the Safety, Efficacy and Pharmacokinetics of GDC-0199 (ABT-199) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients With B-Cell Non-Hodgkin's Lymphoma (NHL) and DLBCL

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 267 (actual)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multicenter, open-label, dose-finding study of venetoclax administered orally in combination with rituximab (R) or obinutuzumab (G) and standard doses of cyclophosphamide, doxorubicin, vincristine and oral prednisone (CHOP) in participants with Non-Hodgkin's Lymphoma (NHL). The study consisted of 2 stages: a dose-finding Phase Ib stage and a Phase II expansion stage. In the Phase I portion of the study, participants were randomized to one of 2 treatment arms venetoclax in combination with R-CHOP (Arm A) and venetoclax in combination with G-CHOP (Arm B) and explored the doses of venetoclax in combination with R-CHOP and G-CHOP. The maximum tolerated dose (MTD) of venetoclax in combination with R-CHOP and G-CHOP was determined during the dose-finding stage. For the Phase II portion of the study, the venetoclax dose for venetoclax + R-CHOP was on a non-continuous dosing schedule as determined by the Phase Ib portion of the study based on safety and tolerability observed in participants treated in the dose escalation portion of the study. On 17 July 2016, Roche/Genentech as the sponsor of Study BO21005 (Goya study), a Phase III study that evaluated G CHOP versus R-CHOP in 1L DLBCL, informed through a press release that the primary endpoint of investigator-assessed PFS was not met. Given these results, Arm B (venetoclax + G-CHOP) was not expanded in Phase II in patients who are first-line with DLBCL.

Conditions

• Lymphoma, Non-Hodgkin

Interventions

Type	Name	Description
DRUG	Venetoclax	Venetoclax 200 to 800 milligrams (mg) tablets will be administered orally once daily (QD) on Days 4-10 of Cycle 1 and Days 1-10 of Cycles 2-8 during Phase I and MTD will be administered according to the same schedule during Phase II.
DRUG	Cyclophosphamide	Cyclophosphamide 750 milligrams per square meter (mg/m\^2) administered intravenously (IV) on Day 1 of each 21-day cycle up to Cycle 6.
DRUG	Obinutuzumab	Obinutuzumab will be administered by IV infusion as an absolute dose of 1000 mg on Days 1, 8, 15 of Cycle 1 and Day 1 of Cycles 2-8 (cycle length = 21 days).
DRUG	Rituximab	Rituximab 375 mg/m\^2 dose will be administered IV on Day 1 of every 21-day cycle.
DRUG	Doxorubicin	Doxorubicin 50 mg/m\^2 administered IV on Day 1 of each 21-day cycle up to Cycle 6.
DRUG	Vincristine	Vincristine 1.4 mg/m\^2 (maximum 2 mg) administered IV on Day 1 of each 21-day cycle up to Cycle 6.
DRUG	Prednisone	Prednisone 100 mg per day orally on Days 1-5 of each 21-day cycle up to Cycle 6.

Timeline

• Start date: 2013-11-17
• Primary completion: 2017-06-28
• Completion: 2019-06-28
• First posted: 2014-02-05
• Last updated: 2020-06-11
• Results posted: 2018-12-20

Locations

52 sites across 10 countries: United States, Australia, Austria, Canada, Czechia, France, Hungary, Italy, Netherlands, Spain

Regulatory

• FDA-regulated drug study