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

NCT04285567 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: CO416852019-003327-372023-504036-17-00
• Study Type: interventional
• Target: 166
• Locations: 5 countries
• Sites: 40

Brief 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).

Conditions

Chronic Lymphocytic Leukemia (CLL)

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease (MRD) Response Rate Measured in Peripheral Blood (PB) Using Next Generation Sequencing (NGS)

  MRD response rate was determined as the percentage of participants with MRD-negativity measured in the PB using NGS using a cutoff of \< 10\^-4. MRD was considered negative if the result was \< 1 CLL cell in 10,000 leukocytes. Percentages have been rounded off to the nearest decimal point.

  At Month 15

Secondary Outcomes (21)

• Progression-free Survival (PFS)

  Up to approximately 56.4 months

• MRD Response Rate in PB of FCR/BR Compared With VEN+G at the End of Treatment Response Visit

  VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)

• MRD Response Rate in Bone Marrow (BM) of FCR/BR Compared With VEN+G at the End of Treatment Response Visit

  VEN+G: From Cycle 1 Day 1 up to 15 months; FCR/BR: From Cycle 1 Day 1 up to 9 months (1 cycle=28 days)

• Objective Response Rate (ORR)

  At Month 15

• CR Rate

  At Month 15

Study Arms (2)

VEN + G

EXPERIMENTAL

Participants will receive 12 cycles of treatment (each cycle is 28 days). Venetoclax (VEN) will be administered orally, daily, with a 5-week ramp-up period, starting on Cycle 1, Day 22 and administration will continue until the end of Cycle 12. Obinutuzumab (G) will be administered intravenously (IV) on Days 1 (and 2), 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6.

Drug: Obinutuzumab; Drug: Venetoclax

FCR/BR

ACTIVE COMPARATOR

Participants will receive 6 cycles of Fludarabine + Cyclophosphamide + Rituximab (FCR) consisting of a single cycle of a single infusion of rituximab on Day 1 and fludarabine and cyclophosphamide infusions on Days 1-3 of each 28-day cycle or bendamustine (B) as infusions on Days 1 and 2 and a single cycle of rituximab on Day 1 of each 28-day cycle.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Bendamustine

Interventions

Obinutuzumab DRUG

Obinutuzumab 1000 milligrams (mg) will be administered IV on Days 1 (and 2), 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6.

Also known as: Gazyva, RO5072759, GA101

VEN + G

Venetoclax DRUG

Venetoclax 20 mg will be administered orally, once daily starting on Day 22 of Cycle 1 for 7 days, then ramp up from 50 to 400 mg/day during Cycle 2 and continue at 400 mg/day from Day 1 of Cycle 3 till end of Cycle 12.

Also known as: Venclexta, RO5537382, GDC-0199

VEN + G

Fludarabine DRUG

Fludarabine will be administered in a dosage of 25 milligram per meter squared (mg/m\^2), IV, on days 1, 2, and 3 of Cycles 1-6.

FCR/BR

Cyclophosphamide DRUG

Cyclophosphamide will be administered in a dosage of 250 mg/m\^2, IV, on Days 1, 2, and 3 Cycles 1-6.

FCR/BR

Rituximab DRUG

Rituximab will be administered at a dose of 375 mg/m\^2, IV, on Cycle 1, Day 1 followed by 500 mg/m\^2 on Day 1 of Cycles 2-6.

Also known as: MabThera, Rituxan

FCR/BR

Bendamustine DRUG

Bendamustine will be administered at a dose of 90 mg/m\^2, IV, on 2 consecutive days of Cycles 1-6.

Also known as: Treanda, Levact, Ribomustin

FCR/BR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to comply with the study protocol, in the investigator's judgment
• Aged 18 years or older
• Have previously untreated documented Chronic Lymphocytic Leukemia (CLL) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
• CLL requiring treatment according to the iwCLL criteria
• Cumulative Illness Rating Scale (CIRS) score ≤ 6 and creatinine clearance (CrCl) ≥ 70 mL/min
• Hematology values within the following limits, unless cytopenia is caused by the underlying disease (i.e., no evidence of additional bone marrow (BM) dysfunction; e.g., myelodysplastic syndrome, hypoplastic BM):
• Absolute neutrophil count ≥ 1.0 x 109/L, unless there is BM involvement
• Platelet count ≥ 75 x 109/L and more than 7 days since last transfusion, or ≥ 30 x 109/L if there is BM involvement
• Adequate liver function as indicated by a total bilirubin, aspartate aminotransferase, and Alanine transaminase ≤ 2 times the institutional upper limit of normal (ULN) value, unless directly attributable to the participant's CLL
• Life expectancy \>6 months
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm

You may not qualify if:

• Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL)
• Participants with Small Lymphocyclic Lymphoma (SLL) only
• Known central nervous system involvement
• Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
• Detected del(17p) or TP53 mutation (valid test within 6-months from screening is required for randomisation)
• An individual organ/system impairment score of 4 as assessed by the Cumulative Illness Rating Scale (CIRS) definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
• Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• History of prior malignancy
• Participants with infections requiring IV treatment (Grade 3 or 4) within the last 8 weeks prior to enrollment
• Evidence of other clinically significant uncontrolled conditions including but not limited to active or uncontrolled systemic infection (e.g., viral, bacterial, or fungal)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
• Hypersensitivity to fludarabine, bendamustine, cyclophosphamide, rituximab, obinutuzumab, or venetoclax or to any of the excipients (e.g., trehalose)
• Pregnant women and nursing mothers
• Vaccination with a live vaccine ≤ 28 days prior to randomization
• Prisoners or participants who are institutionalized by regulatory or court order or persons who are in dependence to the Sponsor or an investigator

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (40)

Medical Center of Aurora

Aurora, Colorado, 80012, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817, United States

Location

University of Tennessee Medical Center;Office of Clinical Trials

Knoxville, Tennessee, 37920, United States

Location

Oncology & Hematology Associates of Southwest Virginia, Inc._Goldschmidt

Roanoke, Virginia, 24014, United States

Location

Canberra Hospital

Canberra, Australian Capital Territory, 2605, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Port Macquarie - Mid North Coast Cancer Institute

Port Macquarie, New South Wales, 2444, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Health;Haematology Research

Clayton, Victoria, 3168, Australia

Location

Peter MacCallum Cancer Centre;Clinical Haematology

Melbourne, Victoria, 3050, Australia

Location

Northern Hospital;Oncology and/or Hematology

Melbourne, Victoria, 3076, Australia

Location

Hopital Haut Leveque Chu de Bordeaux

Pessac, Aquitaine, 33600, France

Location

Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau;Hématologie et Thérapie Cellulaire

Tours, Indre-et-Loire, 37032, France

Location

Centre Hospitalier de Pérpignan;hématologie

Perpignan, Languedoc-Roussillon, 66046, France

Location

Hopital Claude Huriez - CHU de Lille;service maladies appareil digestif

Lille, Nord, 59037, France

Location

Centre Hospitalier intercommunal de Toulon La Seyne sur Mer

Toulon, Provence-Alpes-Côte d'Azur Region, 83100, France

Location

centre hospitalier lyon sud;Service Hématologie

Pierre-Bénite, Rhône, 69310, France

Location

HENRI MONDOR HOSPITAL;Centre d'investigation clinique

Créteil, Val-de-Marne, 94000, France

Location

Centre Hospitalier Universitaire de Caen Normandie

Caen, 14000, France

Location

Clinique Victor Hugo- CCS du Mans

Le Mans, 72000, France

Location

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86021, France

Location

Centre Hospitalier Universitaire de Reims - Hôpital Robert Debré;Hématologie Clinique

Reims, 51092, France

Location

Instituto Tumori Giovanni Paolo II;ONCOLOGIA MEDICA

Bari, Apulia, 70124, Italy

Location

Ospedale Vito Fazzi;U.O. Ematologia IV Piano Polo Oncologico

Lecce, Apulia, 73100, Italy

Location

Azienda Ospedaliero Universitaria;Ematologia

Modena, Emilia-Romagna, 41125, Italy

Location

Policlinico Umberto I

Rome, Lazio, 161, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Rome, Lazio, 168, Italy

Location

Ospedale San Martino;U.O. Clinica Ematologica

Genoa, Liguria, 16132, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico;U.O.C Ematologia

Milan, Lombardy, 20122, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda;Ematologia

Milan, Lombardy, 20162, Italy

Location

Azienda Ospedaliero Universitaria Maggiore della Carità;SCDU Ematologia

Novara, Piedmont, 28100, Italy

Location

AO Santa Maria della Misericordia

Perugia, Umbria, 6132, Italy

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona, 8916, Spain

Location

COMPLEJO HOSPITALARIO DE NAVARRA;Servicio de Hematología

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron;Hematology

Barcelona, 8035, Spain

Location

Hospital Universitario La Paz;Hematología

Madrid, 28015, Spain

Location

Hospital General Universitario Morales Meseguer;Hematologia y Oncologia médica

Murcia, 30008, Spain

Location

Hospital Universitario Virgen del Rocío;Unidad Onco-Hematología Pediátrica

Seville, 41009, Spain

Location

Hospital Universitario de Toledo

Toledo, 45007, Spain

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

obinutuzumab; venetoclax; fludarabine; Cyclophosphamide; Rituximab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical trial

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: February 26, 2020
• Study Start: May 28, 2020
• Primary Completion: March 19, 2024
• Study Completion: March 19, 2025
• Last Updated: March 3, 2026
• Results First Posted: April 17, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

FR (11); AU (8); US (4); ES (7); IT (10)