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

NCT02950051 | Completed Phase 3 DMC

• 2 other identifiers: CLL132015-004936-36
• Study Type: interventional
• Target: 926
• Locations: 10 countries
• Sites: 161

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL

Outcome Measures

Primary Outcomes (2)

• 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

  Month 15

• 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

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

Secondary Outcomes (6)

• MRD negativity rate in PB

  Month 15

• MRD levels in PB

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

• MRD levels in bone marrow (BM)

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

• PFS

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

• Overall response rate (ORR)

  Month 3, 9, 13 and 15

Study Arms (4)

Standard chemoimmunotherapy (SCIT)

ACTIVE COMPARATOR

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)

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

Rituximab + Venetoclax (RVe)

EXPERIMENTAL

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

Biological: Rituximab; Drug: Venetoclax

Obinutuzumab + Venetoclax (GVe)

EXPERIMENTAL

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

Drug: Venetoclax; Biological: Obinutuzumab

Obinutuzumab + Ibrutinib + Venetoclax (GIVe)

EXPERIMENTAL

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.

Drug: Venetoclax; Biological: Obinutuzumab; Drug: Ibrutinib

Interventions

Fludarabine DRUG

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

Also known as: Fludura

Standard chemoimmunotherapy (SCIT)

Cyclophosphamide DRUG

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

Also known as: Endoxan

Standard chemoimmunotherapy (SCIT)

Rituximab BIOLOGICAL

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

Also known as: MabThera, Rituxan

Rituximab + Venetoclax (RVe); Standard chemoimmunotherapy (SCIT)

Bendamustine DRUG

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

Also known as: Ribomustin, Levact

Standard chemoimmunotherapy (SCIT)

Venetoclax 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

Also known as: Venclexta, Venclyxto

Obinutuzumab + Ibrutinib + Venetoclax (GIVe); Obinutuzumab + Venetoclax (GVe); Rituximab + Venetoclax (RVe)

Obinutuzumab 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

Also known as: Gazyva, Gazyvaro

Obinutuzumab + Ibrutinib + Venetoclax (GIVe); Obinutuzumab + Venetoclax (GVe)

Ibrutinib DRUG

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

Also known as: Imbruvica

Obinutuzumab + Ibrutinib + Venetoclax (GIVe)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• German CLL Study Group: lead
• Janssen-Cilag Ltd.: collaborator
• Hoffmann-La Roche: collaborator
• AbbVie: collaborator
• Stichting Hemato-Oncologie voor Volwassenen Nederland: collaborator
• Nordic CLL Study Group (NCLLSG): collaborator
• Swiss Cancer Institute: collaborator
• Cancer Trials Ireland: collaborator
• Israeli CLL Study Group: collaborator

Study Sites (161)

Medizinische Universitaet Wien

Vienna, 1090, Austria

Location

Hanusch Hospital

Vienna, 1140, Austria

Location

Wilhelminenspital

Vienna, 1160, Austria

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Algemeen Ziekenhuis St. Jan

Bruges, 8000, Belgium

Location

Jan Yperman Ziekenhuis

Ieper, 8900, Belgium

Location

UZ Gasthuisberg

Leuven, 3000, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

Aalborg University Hospital

Aalborg, 9100, Denmark

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Rigshospitalet/Copenhagen

Copenhagen, 2100, Denmark

Location

Sydvestjysk Sygehus Esbjerg

Esbjerg, 6700, Denmark

Location

University Hospital Herlev

Herlev, 2730, Denmark

Location

Regionshospitalet Holstebro

Holstebro, 7500, Denmark

Location

Odense Universitets Hospital

Odense, 5000, Denmark

Location

Sjællands Universitetshospital

Roskilde, 4000, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

Helsinki University Hospital

Helsinki, 29, Finland

Location

Jyväskylä Central Hospital

Jyväskylä, 40620, Finland

Location

Oulu University Hospital

Oulu, 90029, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Turku University Hospital

Turku, 20521, Finland

Location

Gesundheitszentrum Klinikum St Marien

Amberg, 92224, Germany

Location

Onkologische Schwerpunktpraxis Kurfürstendamm

Berlin, 10707, Germany

Location

Helios-Klinikum Berlin

Berlin, 13125, Germany

Location

ZAHO Bonn

Bonn, 53113, Germany

Location

Ev. Diakonie-Krankenhaus gemeinnuetzige GmbH

Bremen, 28239, Germany

Location

University Hospital of Cologne

Cologne, 50937, Germany

Location

St. -Johannes-Hospital Dortmund

Dortmund, 44137, Germany

Location

Gefos Dortmund mbH

Dortmund, 44379, Germany

Location

BAG Dresden

Dresden, 1307, Germany

Location

Universitaetsklinik Carl Gustav Carus

Dresden, 1307, Germany

Location

Marien Hospital Düsseldorf GmbH

Düsseldorf, 40479, Germany

Location

St. Georg Klinikum Eisenach GmbH

Eisenach, 99817, Germany

Location

Helios Klinikum Erfurt

Erfurt, 99089, Germany

Location

St. Antonius-Hospital

Eschweiler, 52249, Germany

Location

Universitaetsklinikum Essen

Essen, 45122, Germany

Location

Centrum fuer Haematologie und Onkologie Bethanien

Frankfurt, 60389, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

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

Goslar, 38642, Germany

Location

Onkologische Schwerpunktpraxis Göttingen

Göttingen, 37073, Germany

Location

Universitaetsmedizin Göttingen

Göttingen, 37076, Germany

Location

Universitaetsmedizin Greifswald

Greifswald, 17475, Germany

Location

UKE Hamburg

Hamburg, 20246, Germany

Location

OncoResearch Lerchenfeld GmbH

Hamburg, 22081, Germany

Location

EVK Hamm

Hamm, 59063, Germany

Location

MediProjekt GBR

Hanover, 30171, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Marienhospital Herne

Herne, 44625, Germany

Location

Onkologische Schwerpunktpraxis Des. Freier/Sievers, Hildesheim

Hildesheim, 31135, Germany

Location

Universitaetsklinikum Jena

Jena, 7747, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, 67655, Germany

Location

Städt. Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

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

Kassel, 34119, Germany

Location

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, 24105, Germany

Location

InVO-Institut fuer Versorgungsforschung in der Onkologie GbR

Koblenz, 56068, Germany

Location

Tagesklinik Landshut, Dr. Vehling-Kaiser

Landshut, 84028, Germany

Location

Gemeinschaftspraxis Haemato/ Onkologie Lebach

Lebach, 66822, Germany

Location

Onkologische Schwerpunktpraxis Dr. Mueller, Leer

Leer, 26788, Germany

Location

Klinikum Lippe GmbH

Lemgo, 32657, Germany

Location

Gemeinschaftspraxis Haematologie und Onkologie

Magdeburg, 39104, Germany

Location

Universitaetsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

Universitaetsklinik Mainz

Mainz, 55131, Germany

Location

Mannheimer Onkologie Praxis

Mannheim, 68161, Germany

Location

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

Mayen, 56727, Germany

Location

Kliniken Maria Hilf GmbH

Mönchengladbach, 41063, Germany

Location

Stauferklinikum Schwaebisch-Gmuend

Mutlangen, 73557, Germany

Location

MVZ MOP Elisenhof

München, 80335, Germany

Location

Klinikum Schwabing

München, 80804, Germany

Location

Ludwig-Maximilians-Universitaet Muenchen

München, 81377, Germany

Location

Klinikum rechts der Isar

München, 81657, Germany

Location

Haematologische/Onkologische Praxis Neunkirchen

Neunkirchen, 66538, Germany

Location

Studiengesellschaft Onkologie Rhein Ruhr

Oberhausen, 46145, Germany

Location

Gemeinschaftspraxis Dres. Ballo/Boeck

Offenbach, 63065, Germany

Location

Klinik fuer Haematologie und Onkologie

Paderborn, 33098, Germany

Location

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

Location

Krankenhaus der Barmherzigen Brüder

Regensburg, 93049, Germany

Location

OncoPro GbR

Regensburg, 93053, Germany

Location

Universitätsmedizin Rostock

Rostock, 18057, Germany

Location

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

Saarbrücken, 66113, Germany

Location

Leopoldina-Krankenhaus

Schweinfurt, 97422, Germany

Location

ZAHO-Rheinland

Siegburg, 53721, Germany

Location

Marienhospital Stuttgart

Stuttgart, 70199, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

MVZ Weiden GmbH

Weiden, 92637, Germany

Location

Haematologisch-Onkologische Schwerpunktpraxis Dres. Perker/Sandherr, Weilheim

Weilheim, 82362, Germany

Location

Helios Klinikum Wuppertal

Wuppertal, 42283, Germany

Location

Gemeinschaftspraxis Dr. Schlag/Dr. Schoettker

Würzburg, 97080, Germany

Location

Universitaetsklinik Wuerzburg

Würzburg, 97080, Germany

Location

Cork University Hospital

Cork, Ireland

Location

Mater Misericordiae Hospital

Dublin, Dublin 7, Ireland

Location

St. James's Hospital

Dublin, Dublin 8, Ireland

Location

Beaumont Hospital

Dublin, Dublin 9, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

University Hospital Waterford

Waterford, Ireland

Location

Bnai-Zion Medical. Il-Haifa

Haifa, 31048, Israel

Location

Hadassah Ein Kerem

Jerusalem, 91120, Israel

Location

Meir Medicail Center

Kfar Saba, 4428164, Israel

Location

Rabin medical Center

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Souraski Tel-Aviv Medical Center

Tel Aviv, 6423906, Israel

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223GZ, Netherlands

Location

MC Alkmaar

Alkmaar, 1814HB, Netherlands

Location

Meander Medisch Centrum, Amersfoort

Amersfoort, 3813TZ, Netherlands

Location

VUmc, Amsterdam

Amsterdam, 1081HV, Netherlands

Location

NL-Amsterdam-AMC

Amsterdam, 1105AZ, Netherlands

Location

Ziekenhuis Rijnstate

Arnhem, 6815AD, Netherlands

Location

Amphia Ziekenhuis

Breda, 4818CK, Netherlands

Location

IJsselland Ziekenhuis

Capelle aan den IJssel, 2906ZC, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, 2625AD, Netherlands

Location

Deventer ziekenhuizen

Deventer, 7400GC, Netherlands

Location

Albert Schweitzer Ziekenhuis, Dordrecht

Dordrecht, 3318AT, Netherlands

Location

Gelderse Vallei

Ede, 6716RP, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, 5631BM, Netherlands

Location

Medisch Spectrum Twente

Enschede, 7511JX, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, 2803HH, Netherlands

Location

UMCG

Groningen, 9713GZ, Netherlands

Location

Ziekenhuisgroep Twente Hengelo

Hengelo, 7550AM, Netherlands

Location

Tergooi Ziekenhuis

Hilversum, 1213XZ, Netherlands

Location

Spaarne Ziekenhuis

Hoofddorp, 2134TM, Netherlands

Location

Medisch Centrum Leeuwarden Zuid

Leeuwarden, 8934AD, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333RA, Netherlands

Location

Maastricht university medial Center

Maastricht, 6229HX, Netherlands

Location

St. Antonius Ziekehuis

Nieuwegein, 3435CM, Netherlands

Location

Radboud UMC

Nijmegen, 6525GA, Netherlands

Location

Canisius-Wilhelmina ZH

Nijmegen, 6532SZ, Netherlands

Location

Maasstadziekenhuis

Rotterdam, 3079DZ, Netherlands

Location

Antonius Ziekenhuis Sneek

Sneek, 8601ZK, Netherlands

Location

ZorgSaam Zeeuws Vlaanderen

Terneuzen, 4535PA, Netherlands

Location

St. Elisabeth ZH

Tilburg, 5022GC, Netherlands

Location

UMCU

Utrecht, 3584CX, Netherlands

Location

VieCuri loc. Venlo

Venlo, 5912BL, Netherlands

Location

Zaans Medisch Centrum

Zaandam, 1502DV, Netherlands

Location

Isala

Zwolle, 8025AB, Netherlands

Location

Soedra Aelvsborgs Sjukhus

Borås, 50182, Sweden

Location

Falu lasarett

Falun, 79182, Sweden

Location

Hallands hospital - Halmstad

Halmstad, 30185, Sweden

Location

Universitetsjukhuset i Linkoeping

Linköping, 58185, Sweden

Location

Sunderby Hospital

Luleå, 97180, Sweden

Location

Skane University Hospital Lund

Lund, 22185, Sweden

Location

Universitetssjukhuset i Oerebro

Örebro, 70185, Sweden

Location

Akademiska Sjukhuset

Uppsala, 75185, Sweden

Location

Hallands hospital - Varberg

Varberg, 43237, Sweden

Location

Kantonsspital Aarau

Aarau, 5000, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

IOSI, Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital Graubunden

Chur, 7000, Switzerland

Location

Universitaire de Geneve

Geneva, 1211, Switzerland

Location

KSBL Liestal

Liestal, 4410, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Spital Thurgau AG

Münsterlingen, 8596, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

KS Winterthur

Winterthur, 8401, Switzerland

Location

Stadtspital Triemli

Zurich, 8063, Switzerland

Location

Universitaetsspital Zuerich

Zurich, 8091, Switzerland

Location

Related Publications (5)

• 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.

  PMID: 38821083 BACKGROUND

• 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.

  PMID: 37163621 BACKGROUND

• 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.

  PMID: 38620092 DERIVED

• 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.

  PMID: 37172204 DERIVED

• 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.

  PMID: 32601378 DERIVED

Related Links

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

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

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

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

Study Officials

• Barbara Eichhorst, MD, Prof.

  Department I of Internal Medicine, University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: October 31, 2016
• Study Start: December 13, 2016
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: December 30, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (5); IE (6); DK (9); CH (15); DE (70); NL (33); AU (3); SE (9); IL (6); BE (5)