Clinical trial NCT02950051: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Lymphocytic Leukemia
Keywords: CLL
Lead sponsor: German CLL Study Group
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag Ltd.
name: Hoffmann-La Roche
name: AbbVie
name: Stichting Hemato-Oncologie voor Volwassenen Nederland
name: Nordic CLL Study Group (NCLLSG)
name: Swiss Group for Clinical Cancer Research
name: Cancer Trials Ireland
name: Israeli CLL Study Group
First posted: 2016-10-31
Enrollment: 926
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Miminimal residual disease (MRD) negativity rate in peripheral blood (PB)
timeFrame: Month 15
measure: Progression free survival (PFS)
timeFrame: anticipated for January 2023 (after 213 events occured and 73 months after the first patient has been randomized
Secondary outcomes:
measure: MRD negativity rate in PB
timeFrame: Month 15
measure: MRD levels in PB
timeFrame: Month 2, 9, 13 and later time points according to the discretion of the treating physician at local laboratories
measure: MRD levels in bone marrow (BM)
timeFrame: at final restaging (RE): 2 month after the end of the last treatment cycle
measure: PFS
timeFrame: anticipated for January 2023 (after 213 events occured and 73 months after the first patient has been randomized)
measure: Overall response rate (ORR)
timeFrame: Month 3, 9, 13 and 15
measure: Rate of complete responses (CR) / complete responses with incomplete bone marrow recovery(CRi)
timeFrame: 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
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Wien
country: Austria
facility: Hanusch Hospital
city: Wien
country: Austria
facility: Wilhelminenspital
city: Antwerpen
country: Belgium
facility: ZNA Stuivenberg
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis St. Jan
city: Ieper
country: Belgium
facility: Jan Yperman Ziekenhuis
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Roeselare
country: Belgium
facility: AZ Delta
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet/Copenhagen
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus Esbjerg
city: Herlev
country: Denmark
facility: University Hospital Herlev
city: Holstebro
country: Denmark
facility: Regionshospitalet Holstebro
city: Odense
country: Denmark
facility: Odense Universitets Hospital
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Jyväskylä
country: Finland
facility: Jyväskylä Central Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Amberg
country: Germany
facility: Gesundheitszentrum Klinikum St Marien
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Kurfürstendamm
city: Berlin
country: Germany
facility: Helios-Klinikum Berlin
city: Bonn
country: Germany
facility: ZAHO Bonn
city: Bremen
country: Germany
facility: Ev. Diakonie-Krankenhaus gemeinnuetzige GmbH
city: Dortmund
country: Germany
facility: St. -Johannes-Hospital Dortmund
city: Dortmund
country: Germany
facility: Gefos Dortmund mbH
city: Dresden
country: Germany
facility: BAG Dresden
city: Dresden
country: Germany
facility: Universitaetsklinik Carl Gustav Carus
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf GmbH
city: Eisenach
country: Germany
facility: St. Georg Klinikum Eisenach GmbH
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Eschweiler
country: Germany
facility: St. Antonius-Hospital
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: Centrum fuer Haematologie und Onkologie Bethanien
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Goslar
country: Germany
facility: MVZ Onkologische Kooperation Harz, Drs. Tessen/Hoyer/Zahn
city: Greifswald
country: Germany
facility: Universitaetsmedizin Greifswald
city: Göttingen
country: Germany
facility: Onkologische Schwerpunktpraxis Göttingen
city: Göttingen
country: Germany
facility: Universitaetsmedizin Göttingen
city: Hamburg
country: Germany
facility: UKE Hamburg
city: Hamburg
country: Germany
facility: OncoResearch Lerchenfeld GmbH
city: Hamm
country: Germany
facility: EVK Hamm
city: Hannover
country: Germany
facility: MediProjekt GBR
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Herne
country: Germany
facility: Marienhospital Herne
city: Hildesheim
country: Germany
facility: Onkologische Schwerpunktpraxis Des. Freier/Sievers, Hildesheim
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Städt. Klinikum Karlsruhe
city: Kassel
country: Germany
facility: Dres. Siehl / Soeling, Fachaerzte fuer Haematologie und Internistische Onkologie, Kassel
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel
city: Koblenz
country: Germany
facility: InVO-Institut fuer Versorgungsforschung in der Onkologie GbR
city: Köln
country: Germany
facility: University Hospital of Cologne
city: Landshut
country: Germany
facility: Tagesklinik Landshut, Dr. Vehling-Kaiser
city: Lebach
country: Germany
facility: Gemeinschaftspraxis Haemato/ Onkologie Lebach
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. Mueller, Leer
city: Lemgo
country: Germany
facility: Klinikum Lippe GmbH
city: Magdeburg
country: Germany
facility: Gemeinschaftspraxis Haematologie und Onkologie
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitaetsklinik Mainz
city: Mannheim
country: Germany
facility: Mannheimer Onkologie Praxis
city: Mayen
country: Germany
facility: Institut fuer Versorgungsforschung Dr. med. M. Maasberger/ M. Schmitz/ Dr. med. M. T. Keller
city: Mutlangen
country: Germany
facility: Stauferklinikum Schwaebisch-Gmuend
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
city: München
country: Germany
facility: MVZ MOP Elisenhof
city: München
country: Germany
facility: Klinikum Schwabing
city: München
country: Germany
facility: Ludwig-Maximilians-Universitaet Muenchen
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Neunkirchen
country: Germany
facility: Haematologische/Onkologische Praxis Neunkirchen
city: Oberhausen
country: Germany
facility: Studiengesellschaft Onkologie Rhein Ruhr
city: Offenbach
country: Germany
facility: Gemeinschaftspraxis Dres. Ballo/Boeck
city: Paderborn
country: Germany
facility: Klinik fuer Haematologie und Onkologie
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg
city: Regensburg
country: Germany
facility: Krankenhaus der Barmherzigen Brüder
city: Regensburg
country: Germany
facility: OncoPro GbR
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock
city: Saarbrücken
country: Germany
facility: Praxis für Hämatologie und Onkologie Dres. Jacobs/Daus/Schmits
city: Schweinfurt
country: Germany
facility: Leopoldina-Krankenhaus
city: Siegburg
country: Germany
facility: ZAHO-Rheinland
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Weiden
country: Germany
facility: MVZ Weiden GmbH
city: Weilheim
country: Germany
facility: Haematologisch-Onkologische Schwerpunktpraxis Dres. Perker/Sandherr, Weilheim
city: Wuppertal
country: Germany
facility: Helios Klinikum Wuppertal
city: Würzburg
country: Germany
facility: Gemeinschaftspraxis Dr. Schlag/Dr. Schoettker
city: Würzburg
country: Germany
facility: Universitaetsklinik Wuerzburg
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae Hospital
city: Dublin
country: Ireland
facility: St. James's Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Haifa
country: Israel
facility: Bnai-Zion Medical. Il-Haifa
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem
city: Kfar-Saba
country: Israel
facility: Meir Medicail Center
city: Petach-Tikva
country: Israel
facility: Rabin medical Center
city: Rechovot
country: Israel
facility: Kaplan Medical Center
city: Tel-Aviv
country: Israel
facility: Souraski Tel-Aviv Medical Center
city: Alkmaar
country: Netherlands
facility: MC Alkmaar
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum, Amersfoort
city: Amsterdam
country: Netherlands
facility: VUmc, Amsterdam
city: Amsterdam
country: Netherlands
facility: NL-Amsterdam-AMC
city: Arnhem
country: Netherlands
facility: Ziekenhuis Rijnstate
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Capelle aan den Ijssel
country: Netherlands
facility: IJsselland Ziekenhuis
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Deventer
country: Netherlands
facility: Deventer ziekenhuizen
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Dordrecht
city: Ede
country: Netherlands
facility: Gelderse Vallei
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis
city: Groningen
country: Netherlands
facility: UMCG
city: Hengelo
country: Netherlands
facility: Ziekenhuisgroep Twente Hengelo
city: Hilversum
country: Netherlands
facility: Tergooi Ziekenhuis
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden Zuid
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht university medial Center
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekehuis
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina ZH
city: Rotterdam
country: Netherlands
facility: Maasstadziekenhuis
city: s-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Sneek
country: Netherlands
facility: Antonius Ziekenhuis Sneek
city: Terneuzen
country: Netherlands
facility: ZorgSaam Zeeuws Vlaanderen
city: Tilburg
country: Netherlands
facility: St. Elisabeth ZH
city: Utrecht
country: Netherlands
facility: UMCU
city: Venlo
country: Netherlands
facility: VieCuri loc. Venlo
city: Zaandam
country: Netherlands
facility: Zaans Medisch Centrum
city: Zwolle
country: Netherlands
facility: Isala
city: Borås
country: Sweden
facility: Soedra Aelvsborgs Sjukhus
city: Falun
country: Sweden
facility: Falu lasarett
city: Halmstad
country: Sweden
facility: Hallands hospital - Halmstad
city: Linköping
country: Sweden
facility: Universitetsjukhuset i Linkoeping
city: Luleå
country: Sweden
facility: Sunderby Hospital
city: Lund
country: Sweden
facility: Skane University Hospital Lund
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Varberg
country: Sweden
facility: Hallands hospital - Varberg
city: Örebro
country: Sweden
facility: Universitetssjukhuset i Oerebro
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Bellinzona
country: Switzerland
facility: IOSI, Ospedale Regionale Bellinzona e Valli
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubunden
city: Genève
country: Switzerland
facility: Universitaire de Geneve
city: Liestal
country: Switzerland
facility: KSBL Liestal
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Münsterlingen
country: Switzerland
facility: Spital Thurgau AG
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: KS Winterthur
city: Zürich
country: Switzerland
facility: Stadtspital Triemli
city: Zürich
country: Switzerland
facility: Universitaetsspital Zuerich
Study officials:
affiliation: Department I of Internal Medicine, University Hospital Cologne
name: Barbara Eichhorst, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.