Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab + Venetoclax (RVe) Versus Obinutuzumab (GA101) + Venetoclax (GVe) Versus Obinutuzumab + Ibrutinib + Venetoclax (GIVe) in Fit Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without Del(17p) or TP53 Mutation

Summary

The aim of this study is to evaluate if standard chemoimmunotherapy (FCR, BR) in frontline treatment of physically fit CLL patients without del17p or TP 53 mutation can be replaced by combinations of targeted drugs (Venetoclax, Ibrutinib) with anti-CD20-antibodies (Rituximab, Obinutuzumab), which may induce extremely long lasting remissions.

Conditions

• Chronic Lymphocytic Leukemia

Interventions

DRUG

Fludarabine

Fludarabine i.v.: cycles 1-6: 25 mg/m², d1-3, q28d

DRUG

Cyclophosphamide

Cyclophosphamide i.v.: cycles 1-6: 250 mg/m², d1-3, q28d

BIOLOGICAL

Rituximab

Rituximab i.v. (before chemotherapy): cycle 1: 375 mg/m², d0; cycles 2-6: 500 mg/m², d1; q28d

DRUG

Bendamustine

Bendamustine i.v.: cycles 1-6: 90mg/m², d1-2, q28d

DRUG

Venetoclax

Venetoclax p.o. (ramp-up: dose escalation until final dose is reached) cycle 1: 20 mg (2 tabl. at 10 mg), d22-28, q28d cycle 2: 50 mg (1 tabl. at 50 mg), d1-7; 100 mg (1 tabl. at 100 mg), d8-14; 200 mg (2 tabl. at 100 mg), d15-21; 400 mg (4 tabl. at 100 mg), d22-28, q28d cycles 3-12: 400 mg (4 tabl. at 100 mg), d1-28, q28d

BIOLOGICAL

Obinutuzumab

Obinutuzumab i.v. cycle 1: 100 mg, d1; 900 mg, d1(2); 1000 mg, d8+15, q28d cycles 2-6: 1000 mg, d1, q28d

DRUG

Ibrutinib

Ibrutinib p.o. cycles 1-12: 420 mg, d1-28, q28d cycles 13-36: 420 mg, d1-28, q28d

Sponsors & Collaborators

• Janssen-Cilag Ltd.

  collaborator INDUSTRY

• Hoffmann-La Roche

  collaborator INDUSTRY

• AbbVie

  collaborator INDUSTRY

• Stichting Hemato-Oncologie voor Volwassenen Nederland

  collaborator OTHER

• Nordic CLL Study Group (NCLLSG)

  collaborator UNKNOWN

• Swiss Cancer Institute

  collaborator OTHER

• Cancer Trials Ireland

  collaborator NETWORK

• Israeli CLL Study Group

  collaborator UNKNOWN

• German CLL Study Group

  lead OTHER

Principal Investigators

• Barbara Eichhorst, MD, Prof. · Department I of Internal Medicine, University Hospital Cologne

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-12-13

Primary Completion

2024-02-29

Completion

2024-02-29

Countries

• Austria
• Belgium
• Denmark
• Finland
• Germany
• Ireland
• Israel
• Netherlands
• Sweden
• Switzerland

Study Locations