Last updated on June 2018

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


Brief description of study

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.

Detailed Study Description

Chemoimmunotherapy is the standard of care in first-line treatment of CLL patients without del17p or TP 53 mutation; physically fit patients are treated with fludarabine, cyclophosphamide and rituximab (FCR)1. Due to the high risk of severe neutropenias and infections with FCR, bendamustine and rituximab (BR) must be considered in patients aged >65 years.

However, these conventional chemoimmunotherapies are associated with side effects caused by the rather unspecific mode of action of the chemotherapy. Therefore, there is an urgent need for alternatives, especially chemotherapy-free regimens.

In first line treatment of elderly patients with CLL and coexisting conditions, the anti-CD20-antibody obinutuzumab is the new standard therapy. In the CLL11 trial the combination of obinutuzumab with chlorambucil proved to be safe and lead to markedly improved response rates as well as PFS times in comparison to chlorambucil alone or combined with rituximab.

The BCL2 antagonist venetoclax (GDC-0199/ABT-199) showed striking activity with tumor lysis syndrome as dose limiting toxicity in patients with relapsed and refractory CLL. 400 mg venetoclax was determined to be a safe and efficacious dose. Several patients treated with the combination of venetoclax and rituximab in relapsed refractory CLL even achieved MRD negativity. The FDA approved Venetoclax for the treatment of relapsed CLL with 17p/TP53 on 12th April 2016.

Therefore, venetoclax plus CD20-antibody based combinations have the potential to induce higher rates of MRD negativity in frontline therapy of CLL and concomitantly induce lower rates of toxicities so that chemotherapy might be replaced. Furthermore, venetoclax and obinutuzumab demonstrated synergistic activity in a preclinical study of a murine Non-Hodgkin lymphoma xenograft model, and additive activity in a CLL lymph node model. The combination appears tolerable in the firstline treatment of CLL patients with coexisting conditions whilst the toxicity profile of both drugs compares favorably to those of the chemotherapies currently used in the treatment of CLL. Consequently, it should be tested if rituximab can be replaced by obinutuzumab in combination with venetoclax in this trial.

Ibrutinib, a selective, irreversible small molecular inhibitor of Brutons Tyrosine Kinase (BTK), showed excellent responses and a safe toxicity profile9,10, even in combination with BR. Ibrutinib is approved for treatment of relapsed CLL as well as frontline therapy of CLL by the FDA and EMA (April 29th 2016).

The combination of ibrutinib and venetoclax showed synergy in primary CLL cells.

Consequently, the aim of the current trial is to evaluate if chemoimmunotherapy in the frontline treatment of physically fit patients in CLL can be replaced by combinations of these targeted drugs with anti-CD20-antibodies.

Clinical Study Identifier: NCT02950051

Find a site near you

Start Over

ZNA Stuivenberg

Antwerpen, Belgium
  Connect »

BAG Dresden

Dresden, Germany
  Connect »

OncoPro GbR

Regensburg, Germany
  Connect »

ZAHO-Rheinland

Siegburg, Germany
  Connect »

VUmc, Amsterdam

Amsterdam, Netherlands
  Connect »

NL-Amsterdam-AMC

Amsterdam, Netherlands
  Connect »

AZ Delta

Roeselare, Belgium
  Connect »

ZAHO Bonn

Bonn, Germany
  Connect »

UKE Hamburg

Hamburg, Germany
  Connect »

EVK Hamm

Hamm, Germany
  Connect »

MediProjekt GBR

Hannover, Germany
  Connect »

Westpfalz-Klinikum GmbH

Kaiserslautern, Germany
  Connect »

MC Alkmaar

Alkmaar, Netherlands
  Connect »

IJsselland Ziekenhuis

Capelle aan den Ijssel, Netherlands
  Connect »

Deventer ziekenhuizen

Deventer, Netherlands
  Connect »

Maxima Medisch Centrum

Eindhoven, Netherlands
  Connect »

UMCG

Groningen, Netherlands
  Connect »

Tergooi Ziekenhuis

Hilversum, Netherlands
  Connect »

Spaarne Ziekenhuis

Hoofddorp, Netherlands
  Connect »

St. Antonius Ziekehuis

Nieuwegein, Netherlands
  Connect »

Radboud UMC

Nijmegen, Netherlands
  Connect »

Maasstadziekenhuis

Rotterdam, Netherlands
  Connect »

Jeroen Bosch Ziekenhuis

s-Hertogenbosch, Netherlands
  Connect »

St. Elisabeth ZH

Tilburg, Netherlands
  Connect »

UMCU

Utrecht, Netherlands
  Connect »

Isala

Zwolle, Netherlands
  Connect »

KSBL Liestal

Liestal, Switzerland
  Connect »

KS Winterthur

Winterthur, Switzerland
  Connect »

Kliniken Maria Hilf GmbH

Mönchengladbach, Germany
  Connect »

Spital Thurgau AG

Münsterlingen, Switzerland
  Connect »

Stadtspital Triemli

Zürich, Switzerland
  Connect »

Recruitment Status: Open


Brief Description Eligibility Contact Research Team


Receive Emails About New Clinical Trials!

Sign up for our FREE service to receive email notifications when clinical trials are posted in the medical category of interest to you.