Clinical trial NCT01010061: CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1a)
Official title: An Open-label, Multi-center, Three Arm Randomized Study to Investigate the Safety and Efficacy on Progression-free Survival of RO5072759 + Chlorambucil (GClb) Compared to Rituximab + Chlorambucil (RClb) or Chlorambucil (Clb) Alone in Previously Untreated CLL Patients With Comorbidities.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphocytic Leukemia, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: German CLL Study Group
name: Genentech, Inc.
First posted: 2009-11-09
Enrollment: 787
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: This open-label, randomized, 3-arm study will evaluate the efficacy and safety of obinutuzumab (RO5072759) in combination with chlorambucil as compared to rituximab plus chlorambucil or chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia (CLL). Patients will be randomized 2:2:1 to receive a maximum of six 28-day cycles of either RO5072759 (1000 mg intravenous (iv) infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6) plus chlorambucil (0.5 mg/kg orally, days 1 and 15 of cycles 1-6), or rituximab (iv infusion day 1, 375 mg/m\^2 cycle 1, 500 mg/m\^2 cycles 2-6) plus chlorambucil, or chlorambucil alone. Anticipated time on study treatment is \>6 months and follow-up for disease-progression and safety will be at least 5 years. In the US, this trial is sponsored/managed by Genentech.

Detailed description: Protocol BO21004 is divided into 3 separate Unique Protocol IDs for reporting results on clinicaltrials.gov because there are 3 separate primary analyses conducted at different time-points.

* BO21004 (Stage 1a) \[NCT01010061\] includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to chlorambucil (Clb) reported here.
* BO21004 (Stage 1b) \[NCT01998880\] includes the analysis of 2 of the 3 arms rituximab plus chlorambucil (RClb) compared to chlorambucil (Clb) reported separately.
* BO21004 (Stage 2) \[NCT02053610\] includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to rituximab plus chlorambucil (RClb) reported separately.

Eligibility criteria: Inclusion Criteria:

* Adults \>/=18 years
* Documented Cluster of Differentiation Antigen 20 (CD20) + B-Cell Chronic Lymphocytic Lymphoma (B-CLL)
* Previously untreated Chronic Lymphocytic Leukemia (CLL) requiring treatment according to the National Cancer Institute (NCI) criteria
* Total Cumulative Illness Rating Scale (CIRS) \> 6 and/or creatinine clearance \< 70 ml/min

Exclusion Criteria:

* Prior CLL therapy
* Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation)
* History of other malignancy unless the malignancy has been in remission without treatment for \>/=2 years prior to enrolment, and except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, surgically treated low-grade prostate cancer, or ductal carcinoma in situ (DCIS) of the breast treated with lymphectomy alone
* Positive hepatitis serology (HBV, HCV) or positive HIV or Human T Cell Leukemia Virus (HTLV) testing
* Patients with active infection requiring systemic treatment

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Percentage of Participants With Progression Free Survival Events
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
Secondary outcomes:
measure: Progression Free Survival Based on Independent Review Committee (IRC) Data
timeFrame: Randomization to clinical cutoff date of 9 May 2013 (median observation 22.8 months)
measure: Percentage of Participants With Progression Free Survival Events Based on Independent Review Committee (IRC) Data
timeFrame: Randomization to clinical cutoff date of 9 May 2013 (median observation 22.8 months)
measure: Percentage of Participants With End of Treatment Response (EOTR)
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Percentage of Participants With Best Overall Response
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Event Free Survival
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Overall Survival
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Duration of Response
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Percentage of Participants With Molecular Remission at the End of Treatment
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Time to Re-Treatment/New-antileukemic Therapy
timeFrame: Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
measure: Pharmacokinetics of Obinutuzumab (RO5072759) in Combination With Chlorambucil (Clb)
timeFrame: Pre- and post-dose sampling on day 1 of cycles 1-6 (Up to 26.8 months)
measure: European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire Score
timeFrame: Baseline and Cycle 4 Day 1 (Cy4D1)
measure: European Organization for Research and Treatment of Cancer (EORTC) QLQ-CLL16 Questionnaire Score
timeFrame: Baseline and Cycle 4 Day 1 (Cy4D1)
Other outcomes:
Locations:
city: San Diego
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Green Bay
country: United States
state: Wisconsin
city: Waukesha
country: United States
state: Wisconsin
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Rosario
country: Argentina
city: Adelaide
country: Australia
state: New South Wales
city: Gosford
country: Australia
state: New South Wales
city: Kogarah
country: Australia
state: New South Wales
city: Liverpool
country: Australia
state: New South Wales
city: St. Leonards
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Greenslopes
country: Australia
state: Queensland
city: Southport
country: Australia
state: Queensland
city: Woolloongabba
country: Australia
state: Queensland
city: Kurralta Park
country: Australia
state: South Australia
city: Frankston
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Wien
country: Austria
city: Wien
country: Austria
city: Goiania
country: Brazil
state: GO
city: Belo Horizonte
country: Brazil
state: MG
city: Porto Alegre
country: Brazil
state: RS
city: Santo Andre
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Vratsa
country: Bulgaria
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Winnipeg
country: Canada
state: Manitoba
city: Halifax
country: Canada
state: Nova Scotia
city: Barrie
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Rimouski
country: Canada
state: Quebec
city: Zagreb
country: Croatia
city: Brno
country: Czechia
city: Hradec Kralove
country: Czechia
city: Praha 2
country: Czechia
city: Aalborg
country: Denmark
city: København
country: Denmark
city: Odense
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city: Vejle
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city: Århus
country: Denmark
city: Cairo
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city: Tallinn
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city: Tartu
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city: Angers
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city: Bobigny
country: France
city: Caen
country: France
city: Clermont Ferrand
country: France
city: Creteil
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city: Le Mans
country: France
city: Lille
country: France
city: Lyon
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city: Toulouse
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city: Tours
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city: Vandoeuvre Les Nancy
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city: Ahaus
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city: Amberg
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city: Berlin
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city: Bremen
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city: Bremen
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city: Delitzsch
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city: Detmold
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city: Dresden
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city: Dresden
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city: Eschweiler
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city: Frankfurt am Main
country: Germany
city: Frankfurt an der Oder
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city: Frankfurt
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city: Frechen
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city: Freiburg
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city: Giessen
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city: Greifswald
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city: Hamburg
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city: Homburg/Saar
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city: Kempten
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city: Koblenz
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city: Koeln
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city: Kronach
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city: Köln
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city: Landshut
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city: Lebach
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city: Leer
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city: Lemgo
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city: Lörrach
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city: Lüdenscheid
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city: Magedburg
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city: Mainz
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city: Mannheim
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city: Mutlangen
country: Germany
city: München
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city: München
country: Germany
city: München
country: Germany
city: München
country: Germany
city: Neunkirchen/Saar
country: Germany
city: Nürnberg
country: Germany
city: Oldenburg
country: Germany
city: Porta Westfalica
country: Germany
city: Ravensburg
country: Germany
city: Recklinghausen
country: Germany
city: Regensburg
country: Germany
city: Regensburg
country: Germany
city: Rostock
country: Germany
city: Rüsselsheim
country: Germany
city: Saarbruecken
country: Germany
city: Sindelfingen
country: Germany
city: Stuttgart
country: Germany
city: Trier
country: Germany
city: Tübingen
country: Germany
city: Ulm
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Weilheim
country: Germany
city: Wendlingen
country: Germany
city: Witten
country: Germany
city: Worms
country: Germany
city: Wuerzburg
country: Germany
city: Würzburg
country: Germany
city: Hong Kong
country: Hong Kong
city: Cagliari
country: Italy
city: Cosenza
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city: Ferrara
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city: Orbassano
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city: Torino
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city: Aguascalientes
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country: Mexico
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city: Enschede
country: Netherlands
city: Leeuwarden
country: Netherlands
city: Nieuwegein
country: Netherlands
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Targu-mures
country: Romania
city: Kazan
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Penza
country: Russian Federation
city: Perm
country: Russian Federation
city: Rostov-na-donu
country: Russian Federation
city: UFA
country: Russian Federation
city: Bratislava
country: Slovakia
city: Oviedo
country: Spain
state: Asturias
city: Manresa
country: Spain
state: Barcelona
city: Sabadell
country: Spain
state: Barcelona
city: Jerez de La Frontera
country: Spain
state: Cadiz
city: Santander
country: Spain
state: Cantabria
city: San Sebastian
country: Spain
state: Guipuzcoa
city: La Coruna
country: Spain
state: LA Coruña
city: Santiago de Compostela
country: Spain
state: LA Coruña
city: Pamplona
country: Spain
state: Navarra
city: La Laguna
country: Spain
state: Tenerife
city: Gandia
country: Spain
state: Valencia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Jaen
country: Spain
city: Las Palmas
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Malaga
country: Spain
city: Malaga
country: Spain
city: Murcia
country: Spain
city: Murcia
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Toledo
country: Spain
city: Toledo
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Aarau
country: Switzerland
city: Basel
country: Switzerland
city: Bern
country: Switzerland
city: Chur
country: Switzerland
city: Luzern
country: Switzerland
city: St. Gallen
country: Switzerland
city: Zürich
country: Switzerland
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Khon Kaen
country: Thailand
city: Bournemouth
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Canterbury
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Cottingham
country: United Kingdom
city: Edinburgh
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leicester
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Jaramillo S, Agathangelidis A, Schneider C, Bahlo J, Robrecht S, Tausch E, Bloehdorn J, Hoechstetter M, Fischer K, Eichhorst B, Goede V, Hallek M, Dohner H, Rosenquist R, Ghia P, Stamatopoulos K, Stilgenbauer S. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG). Haematologica. 2020 Nov 1;105(11):2598-2607. doi: 10.3324/haematol.2019.231027.
citation: Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
citation: Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dohner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20;370(12):1101-10. doi: 10.1056/NEJMoa1313984. Epub 2014 Jan 8.