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

NCT ID: NCT02950051

Last Updated: 2024-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 926 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-13
• Study Completion Date: 2024-02-29

Brief 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.

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard chemoimmunotherapy (SCIT)

Patients up to age 65: 6 cycles (q28d) of Fludarabine + Cyclophosphamide + Rituximab (FCR)

Patients older than 65 years: 6 cycles (q28d) of Bendamustine + Rituximab (BR)

Group Type: ACTIVE_COMPARATOR

Fludarabine

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Rituximab

Intervention Type: BIOLOGICAL

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

Bendamustine

Intervention Type: DRUG

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

Rituximab + Venetoclax (RVe)

6 cycles (q28d) of RVe + 6 cycles (q28d) of Venetoclax (alone)

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: BIOLOGICAL

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

Venetoclax

Intervention Type: DRUG

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

Obinutuzumab + Venetoclax (GVe)

6 cycles (q28d) of GVe + 6 cycles (q28d) of Venetoclax (alone)

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Obinutuzumab

Intervention Type: BIOLOGICAL

Obinutuzumab i.v.

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

cycles 2-6: 1000 mg, d1, q28d

Obinutuzumab + Ibrutinib + Venetoclax (GIVe)

6 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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Obinutuzumab

Intervention Type: BIOLOGICAL

Obinutuzumab i.v.

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

cycles 2-6: 1000 mg, d1, q28d

Ibrutinib

Intervention Type: DRUG

Ibrutinib p.o.

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

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

Interventions

Fludarabine

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Rituximab

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

Intervention Type: BIOLOGICAL

Bendamustine

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

Intervention Type: 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

Intervention Type: DRUG

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

Intervention Type: BIOLOGICAL

Ibrutinib

Ibrutinib p.o.

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

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

Intervention Type: DRUG

Other Intervention Names

Fludura; Endoxan; MabThera; Rituxan; Ribomustin; Levact; Venclexta; Venclyxto; Gazyva; Gazyvaro; Imbruvica

Eligibility Criteria

Inclusion Criteria

1. Documented CLL requiring treatment according to iwCLL criteria

2. Age at least 18 years

3. Life expectancy ≥ 6 months

4. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

5. 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)

6. 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

7. 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

8. 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

9. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2

Exclusion Criteria

1. 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).

2. Transformation of CLL (Richter transformation)

3. Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of three more concurrent treatments being administered for hemolysis

4. Detected del(17p) or TP53 mutation

5. Patients with a history of PML

6. 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)

7. Urinary outflow obstruction

8. 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

9. Uncontrolled or active infection

10. Patients with known infection with human immunodeficiency virus (HIV)

11. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers

12. 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)

13. History of stroke or intracranial hemorrhage within 6 months prior to registration

14. Use of investigational agents which might interfere with the study drug within 28 days prior to registration

15. Vaccination with live vaccines 28 days prior to registration

16. Major surgery less than 30 days before start of treatment

17. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products

18. Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial

19. 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)

20. Fertile men or women of childbearing potential unless:

1. surgically sterile or ≥ 2 years after the onset of menopause

2. 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

21. Legal incapacity

22. Prisoners or subjects who are institutionalized by regulatory or court order

23. Persons who are in dependence to the sponsor or an investigator

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: collaborator

Stichting Hemato-Oncologie voor Volwassenen Nederland

OTHER

Sponsor Role: collaborator

Nordic CLL Study Group (NCLLSG)

UNKNOWN

Sponsor Role: collaborator

Swiss Cancer Institute

OTHER

Sponsor Role: collaborator

Cancer Trials Ireland

NETWORK

Sponsor Role: collaborator

Israeli CLL Study Group

UNKNOWN

Sponsor Role: collaborator

German CLL Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barbara Eichhorst, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Department I of Internal Medicine, University Hospital Cologne

Locations

Medizinische Universitaet Wien

Vienna, , Austria

Hanusch Hospital

Vienna, , Austria

Wilhelminenspital

Vienna, , Austria

ZNA Stuivenberg

Antwerp, , Belgium

Algemeen Ziekenhuis St. Jan

Bruges, , Belgium

Jan Yperman Ziekenhuis

Ieper, , Belgium

UZ Gasthuisberg

Leuven, , Belgium

AZ Delta

Roeselare, , Belgium

Aalborg University Hospital

Aalborg, , Denmark

Aarhus University Hospital

Aarhus, , Denmark

Rigshospitalet/Copenhagen

Copenhagen, , Denmark

Sydvestjysk Sygehus Esbjerg

Esbjerg, , Denmark

University Hospital Herlev

Herlev, , Denmark

Regionshospitalet Holstebro

Holstebro, , Denmark

Odense Universitets Hospital

Odense, , Denmark

Sjællands Universitetshospital

Roskilde, , Denmark

Vejle Hospital

Vejle, , Denmark

Helsinki University Hospital

Helsinki, , Finland

Jyväskylä Central Hospital

Jyväskylä, , Finland

Oulu University Hospital

Oulu, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

Gesundheitszentrum Klinikum St Marien

Amberg, , Germany

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, , Germany

Helios-Klinikum Berlin

Berlin, , Germany

ZAHO Bonn

Bonn, , Germany

Ev. Diakonie-Krankenhaus gemeinnuetzige GmbH

Bremen, , Germany

University Hospital of Cologne

Cologne, , Germany

St. -Johannes-Hospital Dortmund

Dortmund, , Germany

Gefos Dortmund mbH

Dortmund, , Germany

BAG Dresden

Dresden, , Germany

Universitaetsklinik Carl Gustav Carus

Dresden, , Germany

Marien Hospital Düsseldorf GmbH

Düsseldorf, , Germany

St. Georg Klinikum Eisenach GmbH

Eisenach, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

St. Antonius-Hospital

Eschweiler, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Centrum fuer Haematologie und Onkologie Bethanien

Frankfurt, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

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

Goslar, , Germany

Onkologische Schwerpunktpraxis Göttingen

Göttingen, , Germany

Universitaetsmedizin Göttingen

Göttingen, , Germany

Universitaetsmedizin Greifswald

Greifswald, , Germany

UKE Hamburg

Hamburg, , Germany

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

EVK Hamm

Hamm, , Germany

MediProjekt GBR

Hanover, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Marienhospital Herne

Herne, , Germany

Onkologische Schwerpunktpraxis Des. Freier/Sievers, Hildesheim

Hildesheim, , Germany

Universitaetsklinikum Jena

Jena, , Germany

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Städt. Klinikum Karlsruhe

Karlsruhe, , Germany

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

Kassel, , Germany

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, , Germany

InVO-Institut fuer Versorgungsforschung in der Onkologie GbR

Koblenz, , Germany

Tagesklinik Landshut, Dr. Vehling-Kaiser

Landshut, , Germany

Gemeinschaftspraxis Haemato/ Onkologie Lebach

Lebach, , Germany

Onkologische Schwerpunktpraxis Dr. Mueller, Leer

Leer, , Germany

Klinikum Lippe GmbH

Lemgo, , Germany

Gemeinschaftspraxis Haematologie und Onkologie

Magdeburg, , Germany

Universitaetsklinikum Magdeburg

Magdeburg, , Germany

Universitaetsklinik Mainz

Mainz, , Germany

Mannheimer Onkologie Praxis

Mannheim, , Germany

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

Mayen, , Germany

Kliniken Maria Hilf GmbH

Mönchengladbach, , Germany

Stauferklinikum Schwaebisch-Gmuend

Mutlangen, , Germany

MVZ MOP Elisenhof

München, , Germany

Klinikum Schwabing

München, , Germany

Ludwig-Maximilians-Universitaet Muenchen

München, , Germany

Klinikum rechts der Isar

München, , Germany

Haematologische/Onkologische Praxis Neunkirchen

Neunkirchen, , Germany

Studiengesellschaft Onkologie Rhein Ruhr

Oberhausen, , Germany

Gemeinschaftspraxis Dres. Ballo/Boeck

Offenbach, , Germany

Klinik fuer Haematologie und Onkologie

Paderborn, , Germany

Studienzentrum Onkologie Ravensburg

Ravensburg, , Germany

Krankenhaus der Barmherzigen Brüder

Regensburg, , Germany

OncoPro GbR

Regensburg, , Germany

Universitätsmedizin Rostock

Rostock, , Germany

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

Saarbrücken, , Germany

Leopoldina-Krankenhaus

Schweinfurt, , Germany

ZAHO-Rheinland

Siegburg, , Germany

Marienhospital Stuttgart

Stuttgart, , Germany

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Universitaetsklinikum Ulm

Ulm, , Germany

MVZ Weiden GmbH

Weiden, , Germany

Haematologisch-Onkologische Schwerpunktpraxis Dres. Perker/Sandherr, Weilheim

Weilheim, , Germany

Helios Klinikum Wuppertal

Wuppertal, , Germany

Gemeinschaftspraxis Dr. Schlag/Dr. Schoettker

Würzburg, , Germany

Universitaetsklinik Wuerzburg

Würzburg, , Germany

Cork University Hospital

Cork, , Ireland

Mater Misericordiae Hospital

Dublin, , Ireland

St. James's Hospital

Dublin, , Ireland

Beaumont Hospital

Dublin, , Ireland

University Hospital Galway

Galway, , Ireland

University Hospital Waterford

Waterford, , Ireland

Bnai-Zion Medical. Il-Haifa

Haifa, , Israel

Hadassah Ein Kerem

Jerusalem, , Israel

Meir Medicail Center

Kfar Saba, , Israel

Rabin medical Center

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Souraski Tel-Aviv Medical Center

Tel Aviv, , Israel

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

MC Alkmaar

Alkmaar, , Netherlands

Meander Medisch Centrum, Amersfoort

Amersfoort, , Netherlands

VUmc, Amsterdam

Amsterdam, , Netherlands

NL-Amsterdam-AMC

Amsterdam, , Netherlands

Ziekenhuis Rijnstate

Arnhem, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

IJsselland Ziekenhuis

Capelle aan den IJssel, , Netherlands

Reinier de Graaf Gasthuis

Delft, , Netherlands

Deventer ziekenhuizen

Deventer, , Netherlands

Albert Schweitzer Ziekenhuis, Dordrecht

Dordrecht, , Netherlands

Gelderse Vallei

Ede, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

Groene Hart Ziekenhuis

Gouda, , Netherlands

UMCG

Groningen, , Netherlands

Ziekenhuisgroep Twente Hengelo

Hengelo, , Netherlands

Tergooi Ziekenhuis

Hilversum, , Netherlands

Spaarne Ziekenhuis

Hoofddorp, , Netherlands

Medisch Centrum Leeuwarden Zuid

Leeuwarden, , Netherlands

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Maastricht university medial Center

Maastricht, , Netherlands

St. Antonius Ziekehuis

Nieuwegein, , Netherlands

Radboud UMC

Nijmegen, , Netherlands

Canisius-Wilhelmina ZH

Nijmegen, , Netherlands

Maasstadziekenhuis

Rotterdam, , Netherlands

Antonius Ziekenhuis Sneek

Sneek, , Netherlands

ZorgSaam Zeeuws Vlaanderen

Terneuzen, , Netherlands

St. Elisabeth ZH

Tilburg, , Netherlands

UMCU

Utrecht, , Netherlands

VieCuri loc. Venlo

Venlo, , Netherlands

Zaans Medisch Centrum

Zaandam, , Netherlands

Isala

Zwolle, , Netherlands

Soedra Aelvsborgs Sjukhus

Borås, , Sweden

Falu lasarett

Falun, , Sweden

Hallands hospital - Halmstad

Halmstad, , Sweden

Universitetsjukhuset i Linkoeping

Linköping, , Sweden

Sunderby Hospital

Luleå, , Sweden

Skane University Hospital Lund

Lund, , Sweden

Universitetssjukhuset i Oerebro

Örebro, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Hallands hospital - Varberg

Varberg, , Sweden

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Universitaetsspital Basel

Basel, , Switzerland

IOSI, Ospedale Regionale Bellinzona e Valli

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Kantonsspital Graubunden

Chur, , Switzerland

Universitaire de Geneve

Geneva, , Switzerland

KSBL Liestal

Liestal, , Switzerland

Luzerner Kantonsspital

Lucerne, , Switzerland

Spital Thurgau AG

Münsterlingen, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

KS Winterthur

Winterthur, , Switzerland

Stadtspital Triemli

Zurich, , Switzerland

Universitaetsspital Zuerich

Zurich, , Switzerland

Countries

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

References

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.

Reference Type: BACKGROUND

PMID: 38821083 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37163621 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38620092 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37172204 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32601378 (View on PubMed)

Related Links

https://www.dcllsg.com/cll13/

Click here for more information about this study: CLL13 (German CLL Study Group)

Other Identifiers

2015-004936-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLL13

Identifier Type: -

Identifier Source: org_study_id