CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1a)

NCT ID: NCT01010061

Last Updated: 2018-09-14

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

787 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-21

Study Completion Date

2017-08-23

Brief Summary

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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

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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.

Conditions

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Lymphocytic Leukemia, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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obinutuzumab + chlorambucil (GClb)

Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 \[first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment\], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).

Group Type EXPERIMENTAL

obinutuzumab

Intervention Type DRUG

1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 \[first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment\], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles).

chlorambucil

Intervention Type DRUG

Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle.

rituximab + chlorambucil (RClb)

Participants received 375 mg/m\^2 rituximab IV infusion on Day 1 of Cycle 1 then 500 mg/m\^2 IV infusions on Day 1 of Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 cycles).

Group Type ACTIVE_COMPARATOR

rituximab

Intervention Type DRUG

375 mg/m\^2 rituximab intravenous (IV) infusion on Day 1 of Cycle 1 (Cycle duration is 28 days) then 500 mg/m\^2 IV infusions on Day 1 of Cycles 2-6.

chlorambucil

Intervention Type DRUG

Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle.

Chlorambucil (Clb)

Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.

Group Type ACTIVE_COMPARATOR

chlorambucil

Intervention Type DRUG

Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle.

Interventions

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obinutuzumab

1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 \[first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment\], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles).

Intervention Type DRUG

rituximab

375 mg/m\^2 rituximab intravenous (IV) infusion on Day 1 of Cycle 1 (Cycle duration is 28 days) then 500 mg/m\^2 IV infusions on Day 1 of Cycles 2-6.

Intervention Type DRUG

chlorambucil

Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle.

Intervention Type DRUG

Other Intervention Names

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RO5072759 GA101 GAZYVA® Rituxan® MabThera®

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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German CLL Study Group

OTHER

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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San Diego, California, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Green Bay, Wisconsin, United States

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Waukesha, Wisconsin, United States

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Buenos Aires, , Argentina

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Rosario, , Argentina

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Adelaide, New South Wales, Australia

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Gosford, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Liverpool, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Sydney, New South Wales, Australia

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Greenslopes, Queensland, Australia

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Southport, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Kurralta Park, South Australia, Australia

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Frankston, Victoria, Australia

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Melbourne, Victoria, Australia

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Graz, , Austria

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Innsbruck, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Goiânia, Goiás, Brazil

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Belo Horizonte, Minas Gerais, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Santo André, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Vratsa, , Bulgaria

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Winnipeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Barrie, Ontario, Canada

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Ottawa, Ontario, Canada

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Montreal, Quebec, Canada

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Rimouski, Quebec, Canada

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Zagreb, , Croatia

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Brno, , Czechia

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Hradec Králové, , Czechia

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Prague, , Czechia

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Aalborg, , Denmark

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Aarhus, , Denmark

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Copenhagen, , Denmark

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Odense, , Denmark

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Vejle, , Denmark

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Cairo, , Egypt

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Tallinn, , Estonia

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Tartu, , Estonia

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Angers, , France

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Bobigny, , France

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Caen, , France

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Clermont-Ferrand, , France

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Créteil, , France

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Le Mans, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Pessac, , France

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Pierre-Bénite, , France

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Poitiers, , France

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Reims, , France

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Rennes, , France

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Rouen, , France

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Toulouse, , France

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Tours, , France

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Vandœuvre-lès-Nancy, , France

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Ahaus, , Germany

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Amberg, , Germany

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Ansbach, , Germany

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Bamberg, , Germany

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Berlin, , Germany

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Bonn, , Germany

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Bremen, , Germany

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Bremen, , Germany

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Bremen, , Germany

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Cologne, , Germany

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Cologne, , Germany

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Delitzsch, , Germany

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Detmold, , Germany

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Dresden, , Germany

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Dresden, , Germany

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Duisburg, , Germany

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Erlangen, , Germany

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Erlangen, , Germany

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Eschweiler, , Germany

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Essen, , Germany

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Essen, , Germany

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Esslingen am Neckar, , Germany

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Frankfurt, , Germany

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Frankfurt (Oder), , Germany

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Frankfurt am Main, , Germany

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Frechen, , Germany

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Freiburg im Breisgau, , Germany

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Giessen, , Germany

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Göttingen, , Germany

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Greifswald, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamburg, , Germany

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Hamm, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Homburg/Saar, , Germany

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Kaiserslautern, , Germany

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Karlsruhe, , Germany

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Kempten, , Germany

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Kiel, , Germany

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Koblenz, , Germany

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Kronach, , Germany

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Landshut, , Germany

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Lebach, , Germany

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Leer, , Germany

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Lemgo, , Germany

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Loerrach, , Germany

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Lüdenscheid, , Germany

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Magedburg, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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Mutlangen, , Germany

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München, , Germany

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München, , Germany

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München, , Germany

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München, , Germany

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München, , Germany

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Neunkirchen/Saar, , Germany

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Nuremberg, , Germany

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Oldenburg, , Germany

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Porta Westfalica, , Germany

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Ravensburg, , Germany

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Recklinghausen, , Germany

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Regensburg, , Germany

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Regensburg, , Germany

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Rostock, , Germany

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Rüsselsheim am Main, , Germany

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Saarbrücken, , Germany

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Sindelfingen, , Germany

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Stuttgart, , Germany

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Trier, , Germany

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Tübingen, , Germany

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Ulm, , Germany

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Villingen-Schwenningen, , Germany

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Weilheim, , Germany

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Wendlingen, , Germany

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Witten, , Germany

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Worms, , Germany

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Würzburg, , Germany

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Hong Kong, , Hong Kong

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Cagliari, , Italy

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Cosenza, , Italy

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Ferrara, , Italy

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Genova, , Italy

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Messina, , Italy

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Modena, , Italy

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Roma, , Italy

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Terni, , Italy

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Torino, , Italy

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Aguascalientes, , Mexico

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Culiacán, , Mexico

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Hermosillo, , Mexico

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Monterrey, , Mexico

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San Luis Potosí City, , Mexico

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Delftzijl, , Netherlands

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Enschede, , Netherlands

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Leeuwarden, , Netherlands

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Nieuwegein, , Netherlands

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Bucharest, , Romania

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Bucharest, , Romania

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Târgu Mureş, , Romania

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Kazan', , Russia

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Nizhny Novgorod, , Russia

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Penza, , Russia

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Perm, , Russia

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Rostov-on-Don, , Russia

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Ufa, , Russia

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Bratislava, , Slovakia

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Manresa, Barcelona, Spain

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Sabadell, Barcelona, Spain

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Jerez de la Frontera, Cadiz, Spain

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Santander, Cantabria, Spain

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Donostia / San Sebastian, Guipuzcoa, Spain

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A Coruña, LA Coruña, Spain

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Santiago de Compostela, LA Coruña, Spain

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Pamplona, Navarre, Spain

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Oviedo, Principality of Asturias, Spain

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San Cristóbal de La Laguna, Tenerife, Spain

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Gandia, Valencia, Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Jaén, , Spain

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Las Palmas, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Málaga, , Spain

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Murcia, , Spain

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Murcia, , Spain

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Salamanca, , Spain

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Seville, , Spain

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Toledo, , Spain

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Toledo, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Aarau, , Switzerland

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Basel, , Switzerland

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Bern, , Switzerland

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Chur, , Switzerland

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Lucerne, , Switzerland

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Sankt Gallen, , Switzerland

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Zurich, , Switzerland

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Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Khon Kaen, , Thailand

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Bournemouth, , United Kingdom

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Cambridge, , United Kingdom

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Canterbury, , United Kingdom

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Cardiff, , United Kingdom

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Cottingham, , United Kingdom

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Edinburgh, , United Kingdom

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Glasgow, , United Kingdom

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Leicester, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Nottingham, , United Kingdom

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Sutton, , United Kingdom

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Countries

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United States Argentina Australia Austria Brazil Bulgaria Canada Croatia Czechia Denmark Egypt Estonia France Germany Hong Kong Italy Mexico Netherlands New Zealand Romania Russia Slovakia Spain Switzerland Thailand United Kingdom

References

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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)

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.

Reference Type DERIVED
PMID: 33131249 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31050355 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24401022 (View on PubMed)

Other Identifiers

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2009-012476-28; CLL11

Identifier Type: -

Identifier Source: secondary_id

BO21004 (Stage 1a)

Identifier Type: -

Identifier Source: org_study_id

NCT02035462

Identifier Type: -

Identifier Source: nct_alias

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