A Study to Compare the Efficacy and Safety of a Combined Regimen of Venetoclax and Obinutuzumab Versus Fludarabine, Cyclophosphamide, and Rituximab (FCR)/ Bendamustine And Rituximab (BR) in FIT Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without DEL (17P) or TP53 Mutation

Summary

This study will evaluate the efficacy and safety of venetoclax and obinutuzumab (VEN + G) compared with fludarabine + cyclophosphamide + rituximab or bendamustine + rituximab (FCR/BR) in FIT participants (FIT is defined by a cumulative illness rating scale \[CIRS\]/score of ≤6 and a normal creatinine clearance of ≥70 mL/min) with previously untreated CLL without DEL(17P) or TP53 mutation requiring treatment. Eligible participants will be randomly assigned in a 1:1 ratio to receive either VEN + G (Arm A) or FCR/BR (Arm B).

Timeline

Start

2020-05-28

Primary completion

2024-03-19

Completion

2025-03-19

Outcome

Met primary endpoint

paper The primary end point was met: 81.3% (VenO) and 54.7% (FCR/BR) achieved uMRD PMID 41770817 ↗

registry Arm A: VEN+G vs Arm B: FCR/BR; p = 0.0004; Difference in Rates 26.60 (95% CI 12.33 to 40.87) NCT04285567 ↗

Publications

• Sharman JP, Laurenti L, Ferrant E, Casado Montero LF, Mulligan SP, Harrup R, Opat S, Ibatici A, Marasca R, Sportoletti P, Thadani-Mulero M, Cazares O, Huang W, Jiang Y, Clark E, Jin HY, Boyer M, Morschhauser F. Fixed-duration VenO vs FCR/BR in fit patients with untreated CLL: primary analysis of the phase 3 CRISTALLO trial. Blood. 2026 Jun 11;147(24):2895-2904. doi: 10.1182/blood.2025030630.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Bendamustine	Small molecule	90 mg/m2	Intravenous
Comparator	Cyclophosphamide	Other / unclassified	250 mg/m2	Intravenous
Comparator	Fludarabine	Small molecule	25 mg/m2	Intravenous
Subject	Obinutuzumab	Monoclonal antibody	1000 mg	Intravenous
Comparator	Rituximab	Monoclonal antibody	500 mg/m2	Intravenous
Subject	Venetoclax	Small molecule	400 mg	Oral

Indications