AzTrials
AzTrials

Chronic Lymphocytic LeukemiaPhase 3GAIANCT02950051

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

A Phase 3 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 161 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Fludarabine, Cyclophosphamide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
926 participants
Where
161 sitesin 10 countries
Study dates
13 Dec 2016to 29 Feb 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented CLL requiring treatment according to iwCLL criteria
  • Age at least 18 years
  • Life expectancy ≥ 6 months
  • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
  • Adequate bone marrow function indicated by a platelet count >30 x10^9/l (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy)
  • Creatinine clearance ≥70ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight) / (72 x creatinine), for women x 0, 85). For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 70 ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min
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  • Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL or to Gilbert's Syndrome
  • Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 12 months after last treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration
  • Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2

Who cannot join

  • Any prior CLL-specific therapies (except corticosteroid treatment administere due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents of 20 mg prednisolone are permitted).
  • Transformation of CLL (Richter transformation)
  • Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of three more concurrent treatments being administered for hemolysis
  • Detected del(17p) or TP53 mutation
  • Patients with a history of PML
  • Any comorbidity or organ system impairment rated with a single CIRS (cumulative illness rating scale) score of 4 (excluding the eyes/ears/nose/throat/larynx organ system), a total CIRS score of more than 6 or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could comprise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract)
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  • Urinary outflow obstruction
  • Malignancies other than CLL currently requiring systemic therapies, not being treated in curative intention before (unless the malignant disease is in a stable remission due to the discretion of the treating physician) or showing signs of progression after curative treatment
  • Uncontrolled or active infection
  • Patients with known infection with human immunodeficiency virus (HIV)
  • Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers
  • Anticoagulant therapy with warfarin or phenoprocoumon, (rotation to alternative anticoagulation is allowed, but note that patients being treated with NOAKs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib)
  • History of stroke or intracranial hemorrhage within 6 months prior to registration
  • Use of investigational agents which might interfere with the study drug within 28 days prior to registration
  • Vaccination with live vaccines 28 days prior to registration
  • Major surgery less than 30 days before start of treatment
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products
  • Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial
  • Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly)
  • Fertile men or women of childbearing potential unless:
  • surgically sterile or ≥ 2 years after the onset of menopause
  • willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment
  • Legal incapacity
  • Prisoners or subjects who are institutionalized by regulatory or court order
  • Persons who are in dependence to the sponsor or an investigator

Trial locations and contacts

161 sites in 10 countries.

161 sites in 10 countries

Germany70 sites

  • Gesundheitszentrum Klinikum St Marien

    Amberg, 92224

  • Onkologische Schwerpunktpraxis Kurfürstendamm

    Berlin, 10707

  • Helios-Klinikum Berlin

    Berlin, 13125

  • ZAHO Bonn

    Bonn, 53113

  • Ev. Diakonie-Krankenhaus gemeinnuetzige GmbH

    Bremen, 28239

  • University Hospital of Cologne

    Cologne, 50937

  • St. -Johannes-Hospital Dortmund

    Dortmund, 44137

  • Gefos Dortmund mbH

    Dortmund, 44379

  • BAG Dresden

    Dresden, 1307

  • Universitaetsklinik Carl Gustav Carus

    Dresden, 1307

  • Marien Hospital Düsseldorf GmbH

    Düsseldorf, 40479

  • St. Georg Klinikum Eisenach GmbH

    Eisenach, 99817

  • Helios Klinikum Erfurt

    Erfurt, 99089

  • St. Antonius-Hospital

    Eschweiler, 52249

  • Universitaetsklinikum Essen

    Essen, 45122

  • Centrum fuer Haematologie und Onkologie Bethanien

    Frankfurt, 60389

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • MVZ Onkologische Kooperation Harz, Drs. Tessen/Hoyer/Zahn

    Goslar, 38642

  • Onkologische Schwerpunktpraxis Göttingen

    Göttingen, 37073

  • Universitaetsmedizin Göttingen

    Göttingen, 37076

  • Universitaetsmedizin Greifswald

    Greifswald, 17475

  • UKE Hamburg

    Hamburg, 20246

  • OncoResearch Lerchenfeld GmbH

    Hamburg, 22081

  • EVK Hamm

    Hamm, 59063

  • MediProjekt GBR

    Hanover, 30171

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitaetsklinikum Heidelberg

    Heidelberg, 69120

  • Marienhospital Herne

    Herne, 44625

  • Onkologische Schwerpunktpraxis Des. Freier/Sievers, Hildesheim

    Hildesheim, 31135

  • Universitaetsklinikum Jena

    Jena, 7747

  • Westpfalz-Klinikum GmbH

    Kaiserslautern, 67655

  • Städt. Klinikum Karlsruhe

    Karlsruhe, 76133

  • Dres. Siehl / Soeling, Fachaerzte fuer Haematologie und Internistische Onkologie, Kassel

    Kassel, 34119

  • Universitaetsklinikum Schleswig-Holstein Campus Kiel

    Kiel, 24105

  • InVO-Institut fuer Versorgungsforschung in der Onkologie GbR

    Koblenz, 56068

  • Tagesklinik Landshut, Dr. Vehling-Kaiser

    Landshut, 84028

  • Gemeinschaftspraxis Haemato/ Onkologie Lebach

    Lebach, 66822

  • Onkologische Schwerpunktpraxis Dr. Mueller, Leer

    Leer, 26788

  • Klinikum Lippe GmbH

    Lemgo, 32657

  • Gemeinschaftspraxis Haematologie und Onkologie

    Magdeburg, 39104

  • Universitaetsklinikum Magdeburg

    Magdeburg, 39120

  • Universitaetsklinik Mainz

    Mainz, 55131

  • Mannheimer Onkologie Praxis

    Mannheim, 68161

  • Institut fuer Versorgungsforschung Dr. med. M. Maasberger/ M. Schmitz/ Dr. med. M. T. Keller

    Mayen, 56727

  • Kliniken Maria Hilf GmbH

    Mönchengladbach, 41063

  • MVZ MOP Elisenhof

    München, 80335

  • Klinikum Schwabing

    München, 80804

  • Ludwig-Maximilians-Universitaet Muenchen

    München, 81377

  • Klinikum rechts der Isar

    München, 81657

  • Stauferklinikum Schwaebisch-Gmuend

    Mutlangen, 73557

  • Haematologische/Onkologische Praxis Neunkirchen

    Neunkirchen, 66538

  • Studiengesellschaft Onkologie Rhein Ruhr

    Oberhausen, 46145

  • Gemeinschaftspraxis Dres. Ballo/Boeck

    Offenbach, 63065

  • Klinik fuer Haematologie und Onkologie

    Paderborn, 33098

  • Studienzentrum Onkologie Ravensburg

    Ravensburg, 88212

  • Krankenhaus der Barmherzigen Brüder

    Regensburg, 93049

  • OncoPro GbR

    Regensburg, 93053

  • Universitätsmedizin Rostock

    Rostock, 18057

  • Praxis für Hämatologie und Onkologie Dres. Jacobs/Daus/Schmits

    Saarbrücken, 66113

  • Leopoldina-Krankenhaus

    Schweinfurt, 97422

  • ZAHO-Rheinland

    Siegburg, 53721

  • Marienhospital Stuttgart

    Stuttgart, 70199

  • Robert-Bosch-Krankenhaus

    Stuttgart, 70376

  • Universitaetsklinikum Tuebingen

    Tübingen, 72076

  • Universitaetsklinikum Ulm

    Ulm, 89081

  • MVZ Weiden GmbH

    Weiden, 92637

  • Haematologisch-Onkologische Schwerpunktpraxis Dres. Perker/Sandherr, Weilheim

    Weilheim, 82362

  • Helios Klinikum Wuppertal

    Wuppertal, 42283

  • Gemeinschaftspraxis Dr. Schlag/Dr. Schoettker

    Würzburg, 97080

  • Universitaetsklinik Wuerzburg

    Würzburg, 97080

Other trials in Germany

Netherlands33 sites

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5223GZ

  • MC Alkmaar

    Alkmaar, 1814HB

  • Meander Medisch Centrum, Amersfoort

    Amersfoort, 3813TZ

  • VUmc, Amsterdam

    Amsterdam, 1081HV

  • NL-Amsterdam-AMC

    Amsterdam, 1105AZ

  • Ziekenhuis Rijnstate

    Arnhem, 6815AD

  • Amphia Ziekenhuis

    Breda, 4818CK

  • IJsselland Ziekenhuis

    Capelle aan den IJssel, 2906ZC

  • Reinier de Graaf Gasthuis

    Delft, 2625AD

  • Deventer ziekenhuizen

    Deventer, 7400GC

  • Albert Schweitzer Ziekenhuis, Dordrecht

    Dordrecht, 3318AT

  • Gelderse Vallei

    Ede, 6716RP

  • Maxima Medisch Centrum

    Eindhoven, 5631BM

  • Medisch Spectrum Twente

    Enschede, 7511JX

  • Groene Hart Ziekenhuis

    Gouda, 2803HH

  • UMCG

    Groningen, 9713GZ

  • Ziekenhuisgroep Twente Hengelo

    Hengelo, 7550AM

  • Tergooi Ziekenhuis

    Hilversum, 1213XZ

  • Spaarne Ziekenhuis

    Hoofddorp, 2134TM

  • Medisch Centrum Leeuwarden Zuid

    Leeuwarden, 8934AD

  • Leids Universitair Medisch Centrum

    Leiden, 2333RA

  • Maastricht university medial Center

    Maastricht, 6229HX

  • St. Antonius Ziekehuis

    Nieuwegein, 3435CM

  • Radboud UMC

    Nijmegen, 6525GA

  • Canisius-Wilhelmina ZH

    Nijmegen, 6532SZ

  • Maasstadziekenhuis

    Rotterdam, 3079DZ

  • Antonius Ziekenhuis Sneek

    Sneek, 8601ZK

  • ZorgSaam Zeeuws Vlaanderen

    Terneuzen, 4535PA

  • St. Elisabeth ZH

    Tilburg, 5022GC

  • UMCU

    Utrecht, 3584CX

  • VieCuri loc. Venlo

    Venlo, 5912BL

  • Zaans Medisch Centrum

    Zaandam, 1502DV

  • Isala

    Zwolle, 8025AB

Other trials in Netherlands

Switzerland15 sites

  • Kantonsspital Aarau

    Aarau, 5000

  • Kantonsspital Baden

    Baden, 5404

  • Universitaetsspital Basel

    Basel, 4031

  • IOSI, Ospedale Regionale Bellinzona e Valli

    Bellinzona, 6500

  • Inselspital Bern

    Bern, 3010

  • Kantonsspital Graubunden

    Chur, 7000

  • Universitaire de Geneve

    Geneva, 1211

  • KSBL Liestal

    Liestal, 4410

  • Luzerner Kantonsspital

    Lucerne, 6000

  • Spital Thurgau AG

    Münsterlingen, 8596

  • Kantonsspital Olten

    Olten, 4600

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • KS Winterthur

    Winterthur, 8401

  • Stadtspital Triemli

    Zurich, 8063

  • Universitaetsspital Zuerich

    Zurich, 8091

Other trials in Switzerland

Denmark9 sites

  • Aalborg University Hospital

    Aalborg, 9100

  • Aarhus University Hospital

    Aarhus, 8000

  • Rigshospitalet/Copenhagen

    Copenhagen, 2100

  • Sydvestjysk Sygehus Esbjerg

    Esbjerg, 6700

  • University Hospital Herlev

    Herlev, 2730

  • Regionshospitalet Holstebro

    Holstebro, 7500

  • Odense Universitets Hospital

    Odense, 5000

  • Sjællands Universitetshospital

    Roskilde, 4000

  • Vejle Hospital

    Vejle, 7100

Other trials in Denmark

Sweden9 sites

  • Soedra Aelvsborgs Sjukhus

    Borås, 50182

  • Falu lasarett

    Falun, 79182

  • Hallands hospital - Halmstad

    Halmstad, 30185

  • Universitetsjukhuset i Linkoeping

    Linköping, 58185

  • Sunderby Hospital

    Luleå, 97180

  • Skane University Hospital Lund

    Lund, 22185

  • Universitetssjukhuset i Oerebro

    Örebro, 70185

  • Akademiska Sjukhuset

    Uppsala, 75185

  • Hallands hospital - Varberg

    Varberg, 43237

Other trials in Sweden

Ireland6 sites

  • Cork University Hospital

    Cork

  • Mater Misericordiae Hospital

    Dublin, Dublin 7

  • St. James's Hospital

    Dublin, Dublin 8

  • Beaumont Hospital

    Dublin, Dublin 9

  • University Hospital Galway

    Galway

  • University Hospital Waterford

    Waterford

Other trials in Ireland

Israel6 sites

  • Bnai-Zion Medical. Il-Haifa

    Haifa, 31048

  • Hadassah Ein Kerem

    Jerusalem, 91120

  • Meir Medicail Center

    Kfar Saba, 4428164

  • Rabin medical Center

    Petah Tikva, 4941492

  • Kaplan Medical Center

    Rehovot, 76100

  • Souraski Tel-Aviv Medical Center

    Tel Aviv, 6423906

Other trials in Israel

Belgium5 sites

  • ZNA Stuivenberg

    Antwerp, 2060

  • Algemeen Ziekenhuis St. Jan

    Bruges, 8000

  • Jan Yperman Ziekenhuis

    Ieper, 8900

  • UZ Gasthuisberg

    Leuven, 3000

  • AZ Delta

    Roeselare, 8800

Other trials in Belgium

Finland5 sites

  • Helsinki University Hospital

    Helsinki, 29

  • Jyväskylä Central Hospital

    Jyväskylä, 40620

  • Oulu University Hospital

    Oulu, 90029

  • Tampere University Hospital

    Tampere, 33520

  • Turku University Hospital

    Turku, 20521

Other trials in Finland

Austria3 sites

  • Medizinische Universitaet Wien

    Vienna, 1090

  • Hanusch Hospital

    Vienna, 1140

  • Wilhelminenspital

    Vienna, 1160

Other trials in Austria

About this study

Official title: A Phase 3 Multicenter, Randomized, Prospective, Open-label Trial of Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab Plus Venetoclax (RVe) Versus Obinutuzumab (GA101) Plus Venetoclax (GVe) Versus Obinutuzumab Plus Ibrutinib Plus Venetoclax (GIVe) in Fit Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without Del(17p) or TP53 Mutation

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.

Read the detailed 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 Bruton´s 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.

Keywords
CLL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludura

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

  • CyclophosphamideDrug

    Also called Endoxan

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

  • RituximabBiological

    Also called MabThera, Rituxan

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

  • BendamustineDrug

    Also called Ribomustin, Levact

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

  • VenetoclaxDrug

    Also called Venclexta, Venclyxto

    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

  • ObinutuzumabBiological

    Also called Gazyva, Gazyvaro

    Obinutuzumab i.v.

    cycle 1: 100 mg, d1; 900 mg, d1(2); 1000 mg, d8+15, q28d

    cycles 2-6: 1000 mg, d1, q28d

  • IbrutinibDrug

    Also called Imbruvica

    Ibrutinib p.o.

    cycles 1-12: 420 mg, d1-28, q28d

    cycles 13-36: 420 mg, d1-28, q28d

Study groups in NCT02950051
Study groupRoleWhat they receive
Standard chemoimmunotherapy (SCIT)Active comparatorPatients up to age 65: 6 cycles (q28d) of Fludarabine + Cyclophosphamide + Rituximab (FCR) Patients older than 65 years: 6 cycles (q28d) of Bendamustine + Rituximab (BR)
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Rituximab; Drug: Bendamustine
Rituximab + Venetoclax (RVe)Experimental6 cycles (q28d) of RVe + 6 cycles (q28d) of Venetoclax (alone)
Receives: Biological: Rituximab; Drug: Venetoclax
Obinutuzumab + Venetoclax (GVe)Experimental6 cycles (q28d) of GVe + 6 cycles (q28d) of Venetoclax (alone)
Receives: Drug: Venetoclax; Biological: Obinutuzumab
Obinutuzumab + Ibrutinib + Venetoclax (GIVe)Experimental6 cycles (q28d) of GIVe + 6 cycles (q28d) of Ibrutinib plus Venetoclax. Administration of ibrutinib will be continued for a maximum of 36 months or until MRD negativity, start of new anti-CLL therapy or inacceptable toxicity, whatever occurs first.
Receives: Drug: Venetoclax; Biological: Obinutuzumab; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Miminimal residual disease (MRD) negativity rate in peripheral blood (PB)

    Proportion of MRD negative patients at month15 based on the intention-to-treat population (ITT population), that is the number of MRD negative patients divided by the number of the ITT population. MRD negativity is defined as <1 CLL-cell among 10,000 leukocytes analyzed [0.01%], i.e. < 10-4.

    Primary outcome measure for the comparison of GVe vs. SCIT

    Measured: Month 15

  2. Progression free survival (PFS)

    Time from randomization to the first occurrence of progression or relapse (determined using standard IWCLL guidelines [2008]), or death from any cause, whichever occurs first.

    Primary outcome measure for the comparison GIVe vs. SCIT

    Measured: anticipated for January 2023 (after 213 events occured and 73 months after the first patient has been randomized

Secondary outcomes (6)

  1. MRD negativity rate in PB

    Time from randomization to the first occurrence of progression or relapse (determined using standard IWCLL guidelines [2008]), or death from any cause, whichever occurs first.

    Secondary outcome measure for all other comparisons with the exception of GVe vs. SCIT

    Measured: Month 15

  2. MRD levels in PB

    Measured: Month 2, 9, 13 and later time points according to the discretion of the treating physician at local laboratories

  3. MRD levels in bone marrow (BM)

    Measured: at final restaging (RE): 2 month after the end of the last treatment cycle

  4. PFS

    Time from randomization to the first occurrence of progression or relapse (determined using standard IWCLL guidelines [2008]), or death from any cause, whichever occurs first.

    Secondary outcome measure for all other comparisons with the exception of GIVe vs.SCIT

    Measured: anticipated for January 2023 (after 213 events occured and 73 months after the first patient has been randomized)

  5. Overall response rate (ORR)

    Measured: Month 3, 9, 13 and 15

  6. Rate of complete responses (CR) / complete responses with incomplete bone marrow recovery(CRi)

    Complete response (CR) rate is defined by the proportion of patients having achieved a CR/CRi defined by the IWCLL guidelines as best response until and including the response assessment at Month 6, 9, 12 and 15 (= number of patients with best response CR/CRi divided by the ITT population).

    Measured: Interim staging (IST: cycle 4 d1), cycle 9 d1 (or final restaging (RE) for patients in the SCIT arm), IR (or three month after RE for patients in the SCIT arm respectively) and Month 15, with regard to best response achieved

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2016 (estimated)
  2. Study start13 Dec 2016
  3. Primary completion29 Feb 2024
  4. Study completion29 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
926 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02950051
Sponsor's protocol ID
CLL13
Other IDs
2015-004936-36, 2015
Acronym
GAIA
Status last verified
Mar 2024
First submitted
27 Oct 2016
Last updated
30 Dec 2024
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Furstenau M, Kater AP, Robrecht S, von Tresckow J, Zhang C, Gregor M, Thornton P, Staber PB, Tadmor T, Lindstrom V, Juliusson G, Janssens A, Levin MD, da Cunha-Bang C, Schneider C, Goldschmidt N, Vandenberghe E, Rossi D, Benz R, Nosslinger T, Heintel D, Poulsen CB, Christiansen I, Frederiksen H, Enggaard L, Posthuma EFM, Issa DE, Visser HPJ, Bellido M, Kutsch N, Durig J, Stehle A, Vohringer M, Bottcher S, Schulte C, Simon F, Fink AM, Fischer K, Holmes EE, Kreuzer KA, Ritgen M, Bruggemann M, Tausch E, Stilgenbauer S, Hallek M, Niemann CU, Eichhorst B. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2024 Jun;25(6):744-759. doi: 10.1016/S1470-2045(24)00196-7.

    PubMed 38821083

  • Eichhorst B, Niemann CU, Kater AP, Furstenau M, von Tresckow J, Zhang C, Robrecht S, Gregor M, Juliusson G, Thornton P, Staber PB, Tadmor T, Lindstrom V, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schottker B, Nosslinger T, Janssens A, Christiansen I, Baumann M, Frederiksen H, van der Klift M, Jager U, Leys MBL, Hoogendoorn M, Lotfi K, Hebart H, Gaska T, Koene H, Enggaard L, Goede J, Regelink JC, Widmer A, Simon F, De Silva N, Fink AM, Bahlo J, Fischer K, Wendtner CM, Kreuzer KA, Ritgen M, Bruggemann M, Tausch E, Levin MD, van Oers M, Geisler C, Stilgenbauer S, Hallek M; GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland. First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia. N Engl J Med. 2023 May 11;388(19):1739-1754. doi: 10.1056/NEJMoa2213093.

    PubMed 37163621

  • Jebaraj BMC, Tausch E, Yosifov DY, Schneider C, Furstenau M, Zhang C, Robrecht S, da Cunha-Bang C, Levin MD, Staber PB, Huber H, Tadmor T, Thornton P, Gregor M, Fink AM, Fischer K, Kreuzer KA, Ritgen M, Hallek MJ, Kater AP, Niemann CU, Eichhorst BF, Stilgenbauer S. Telomere length in chronic lymphocytic leukemia treated with venetoclax-based regimen in GAIA/CLL13 and CLL2-GIVe trials. Blood. 2026 Oct 6:blood.2025032302. doi: 10.1182/blood.2025032302. Online ahead of print.

    PubMed 42837320

  • Furstenau M, Niemann CU, Robrecht S, Rotbain EC, Eurelings L, Giza A, von Tresckow J, Zhang C, Gregor M, Thornton P, Staber PB, Tadmor T, Lindstrom V, Juliusson G, Janssens A, da Cunha-Bang C, Schneider C, Herishanu Y, O'Shea D, Baumann M, Widmer A, Nosslinger T, Poulsen CB, Frederiksen H, Lotfi K, Ranti J, Enggaard L, Velders G, Vekemans MC, de Heer K, Snijders TF, Siemes C, Wendtner CM, Knauf W, Kroeber A, Zahn MO, Illmer T, Schottker B, Simon F, Fink A, Fischer K, D'Brot R, Holmes E, Kreuzer KA, Ritgen M, Bruggemann M, Tausch E, Stilgenbauer S, Levin MD, Hallek M, Kater AP, Eichhorst B. Venetoclax combinations in untreated CLL: 5-year results and patient-reported outcomes analysis of the CLL13/GAIA trial. Blood. 2026 Jun 18;147(25):3025-3038. doi: 10.1182/blood.2025032160.

    PubMed 41911073

  • Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.

    PubMed 38620092

  • Furstenau M, Thus YJ, Robrecht S, Mellink CHM, van der Kevie-Kersemaekers AM, Dubois J, von Tresckow J, Patz M, Gregor M, Thornton P, Staber PB, Tadmor T, Levin MD, da Cunha-Bang C, Schneider C, Poulsen CB, Illmer T, Schottker B, Janssens A, Christiansen I, Nosslinger T, Baumann M, Hebart H, Gaska T, Regelink JC, Dompeling EC, Lindstrom V, Juliusson G, Widmer A, Goede J, Goldschmidt N, Simon F, De Silva N, Fink AM, Fischer K, Wendtner CM, Ritgen M, Bruggemann M, Tausch E, Spaargaren M, Eldering E, Stilgenbauer S, Niemann CU, Hallek M, Eichhorst B, Kreuzer KA, Kater AP. High karyotypic complexity is an independent prognostic factor in patients with CLL treated with venetoclax combinations. Blood. 2023 Aug 3;142(5):446-459. doi: 10.1182/blood.2023019634.

    PubMed 37172204

  • Furstenau M, Langerbeins P, De Silva N, Fink AM, Robrecht S, von Tresckow J, Simon F, Hohloch K, Droogendijk J, van der Klift M, van der Spek E, Illmer T, Schottker B, Fischer K, Wendtner CM, Tausch E, Stilgenbauer S, Niemann CU, Gregor M, Kater AP, Hallek M, Eichhorst B. COVID-19 among fit patients with CLL treated with venetoclax-based combinations. Leukemia. 2020 Aug;34(8):2225-2229. doi: 10.1038/s41375-020-0941-7. Epub 2020 Jun 29. No abstract available.

    PubMed 32601378

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by German CLL Study Group at 161 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 161 sites in Germany, Netherlands, Switzerland, Denmark, Sweden and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Miminimal residual disease (MRD) negativity rate in peripheral blood (PB) (time frame: Month 15). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02950051, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2024.

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