CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 2)

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.

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.

Study Overview

• Status: Completed
• Conditions: Lymphocytic Leukemia, Chronic
• Intervention / Treatment: Drug: obinutuzumab; Drug: chlorambucil; Drug: rituximab

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 separately.
• 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) includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to rituximab plus chlorambucil (RClb) reported here.

• Study Type: Interventional
• Enrollment (Actual): 787
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1406
  • Buenos Aires, Argentina, C1180AAX
  • Buenos Aires, Argentina, 1425
  • Buenos Aires, Argentina, C1114AAN
  • Buenos Aires, Argentina, C1221ADC
  • Buenos Aires, Argentina, C1431FWO
  • Rosario, Argentina, 2000
• Australia
  • New South Wales
    • Adelaide, New South Wales, Australia, 5011
    • Gosford, New South Wales, Australia, 2250
    • Kogarah, New South Wales, Australia, 2217
    • Liverpool, New South Wales, Australia, 2170
    • St. Leonards, New South Wales, Australia, 2065
    • Sydney, New South Wales, Australia, 2139
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
    • Southport, Queensland, Australia, 4215
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
  • Victoria
    • Frankston, Victoria, Australia, 3199
    • Melbourne, Victoria, Australia, 3168
• Austria
  • Graz, Austria, 8036
  • Innsbruck, Austria, 6020
  • Wien, Austria, 1160
  • Wien, Austria, 1090
• Brazil
  • GO
    • Goiania, GO, Brazil, 74140-050
  • MG
    • Belo Horizonte, MG, Brazil, 31270-901
  • RS
    • Porto Alegre, RS, Brazil, 90880-480
  • SP
    • Santo Andre, SP, Brazil, 09060-650
    • Sao Paulo, SP, Brazil, 05403-000
• Bulgaria
  • Pleven, Bulgaria, 5800
  • Plovdiv, Bulgaria, 4002
  • Sofia, Bulgaria, 1756
  • Varna, Bulgaria, 9010
  • Vratsa, Bulgaria, 3000
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
    • Edmonton, Alberta, Canada, T6G 1Z2
  • Manitoba
    • Winnipeg, Manitoba, Canada, R0C 2Z0
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
    • Ottawa, Ontario, Canada, K1H 8L6
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
    • Rimouski, Quebec, Canada, G5L 5T1
• Croatia
  • Zagreb, Croatia, 10000
• Czechia
  • Brno, Czechia, 625 00
  • Hradec Kralove, Czechia, 500 05
  • Praha 2, Czechia, 128 08
• Denmark
  • Aalborg, Denmark, 9000
  • København, Denmark, 2100
  • Odense, Denmark, 5000
  • Vejle, Denmark, 7100
  • Århus, Denmark, 8000
• Egypt
  • Cairo, Egypt, 11796
• Estonia
  • Tallinn, Estonia, 13419
  • Tartu, Estonia, 51014
• France
  • Angers, France, 49933
  • Bobigny, France, 93009
  • Caen, France, 14076
  • Clermont Ferrand, France, 63003
  • Creteil, France, 94010
  • Le Mans, France, 72015
  • Lille, France, 59037
  • Lyon, France, 69373
  • Marseille, France, 13273
  • Montpellier, France, 34295
  • Nantes, France, 44093
  • Paris, France, 75651
  • Paris, France, 75475
  • Pessac, France, 33604
  • Pierre Benite, France, 69495
  • Poitiers, France, 86021
  • Reims, France, 51092
  • Rennes, France, 35033
  • Rouen, France, 76038
  • Toulouse, France, 31059
  • Tours, France, 37044
  • Vandoeuvre Les Nancy, France, 54511
• Germany
  • Ahaus, Germany, 48683
  • Amberg, Germany, 92224
  • Ansbach, Germany, 91522
  • Bamberg, Germany, 96049
  • Berlin, Germany, 12200
  • Bonn, Germany, 53113
  • Bremen, Germany, 28177
  • Bremen, Germany, 28239
  • Bremen, Germany, 28209
  • Delitzsch, Germany, 04509
  • Detmold, Germany, 32756
  • Dresden, Germany, 01307
  • Dresden, Germany, 01127
  • Duisburg, Germany, 47051
  • Erlangen, Germany, 91054
  • Erlangen, Germany, 91052
  • Eschweiler, Germany, 52249
  • Essen, Germany, 45122
  • Essen, Germany, 45239
  • Esslingen, Germany, 73730
  • Frankfurt, Germany, 60596
  • Frankfurt am Main, Germany, 60389
  • Frankfurt an der Oder, Germany, 15236
  • Frechen, Germany, 50226
  • Freiburg, Germany, 79106
  • Giessen, Germany
  • Greifswald, Germany, 17475
  • Göttingen, Germany, 37075
  • Hamburg, Germany, 22081
  • Hamburg, Germany, 20246
  • Hamburg, Germany, 20095
  • Hamburg, Germany, 20099
  • Hamburg, Germany, 22767
  • Hamburg, Germany, 22087
  • Hamm, Germany, 59063
  • Hannover, Germany, 30449
  • Heidelberg, Germany, 69120
  • Homburg/Saar, Germany, 66241
  • Kaiserslautern, Germany, 67655
  • Karlsruhe, Germany, 76133
  • Kempten, Germany, 87439
  • Kiel, Germany, 24116
  • Koblenz, Germany, 56068
  • Koeln, Germany, 50674
  • Kronach, Germany, 96317
  • Köln, Germany, 50924
  • Landshut, Germany, 84028
  • Lebach, Germany, 66822
  • Leer, Germany, 26789
  • Lemgo, Germany, 32657
  • Lörrach, Germany, 79539
  • Lüdenscheid, Germany, 58515
  • Magedburg, Germany, 39104
  • Mainz, Germany, 55131
  • Mannheim, Germany, 68161
  • Muenchen, Germany, 81377
  • Mutlangen, Germany, 73557
  • München, Germany, 81675
  • München, Germany, 80335
  • München, Germany, 81241
  • München, Germany, 81479
  • Neunkirchen/Saar, Germany, 66538
  • Nürnberg, Germany, 90449
  • Oldenburg, Germany, 26121
  • Porta Westfalica, Germany, 32457
  • Ravensburg, Germany, 88212
  • Recklinghausen, Germany, 45657
  • Regensburg, Germany, 93053
  • Regensburg, Germany, 93049
  • Rostock, Germany, 18057
  • Rüsselsheim, Germany, 65428
  • Saarbruecken, Germany, 66113
  • Sindelfingen, Germany, 71065
  • Stuttgart, Germany, 70199
  • Trier, Germany, 54290
  • Tübingen, Germany, 72076
  • Ulm, Germany, 89081
  • Villingen-Schwenningen, Germany, 78052
  • Weilheim, Germany, 82362
  • Wendlingen, Germany, 73240
  • Witten, Germany, 58452
  • Worms, Germany, 67547
  • Wuerzburg, Germany, 97080
  • Würzburg, Germany, 97080
• Hong Kong
  • Hong Kong, Hong Kong
• Italy
  • Calabria
    • Cosenza, Calabria, Italy, 87100
  • Emilia-Romagna
    • Ferrara, Emilia-Romagna, Italy, 44100
    • Modena, Emilia-Romagna, Italy, 41100
  • Lazio
    • Roma, Lazio, Italy, 00144
    • Roma, Lazio, Italy, 00168
    • Roma, Lazio, Italy, 00161
  • Liguria
    • Genova, Liguria, Italy, 16132
  • Lombardia
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20162
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
    • Torino, Piemonte, Italy, 10126
  • Sardegna
    • Cagliari, Sardegna, Italy, 09121
  • Sicilia
    • Messina, Sicilia, Italy, 98165
  • Umbria
    • Terni, Umbria, Italy, 05100
• Mexico
  • Aguascalientes, Mexico, 20127
  • Culiacan, Mexico, 80230
  • Hermosillo, Mexico, 83000
  • Monterrey, Mexico, 64460
  • San Luis Potosi, Mexico, 78218
• Netherlands
  • Delftzijl, Netherlands, 9934 JD
  • Enschede, Netherlands, 7511 JX
  • Leeuwarden, Netherlands, 8934 AD
  • Nieuwegein, Netherlands, 3430 EM
• New Zealand
  • Auckland, New Zealand, 1009
  • Christchurch, New Zealand, 8011
• Romania
  • Bucharest, Romania, 022328
  • Bucuresti, Romania, 030171
  • Targu-mures, Romania, 540136
• Russian Federation
  • Kazan, Russian Federation, 420029
  • Nizhny Novgorod, Russian Federation, 603126
  • Penza, Russian Federation, 440071
  • Perm, Russian Federation, 614077
  • Rostov-na-donu, Russian Federation, 344022
  • UFA, Russian Federation, 450005
• Slovakia
  • Bratislava, Slovakia, 833 10
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08025
  • Jaen, Spain, 23007
  • Las Palmas, Spain, 35020
  • Madrid, Spain, 28006
  • Madrid, Spain, 28046
  • Madrid, Spain, 28034
  • Madrid, Spain, 28905
  • Madrid, Spain, 28041
  • Madrid, Spain, 28222
  • Madrid, Spain, 28033
  • Madrid, Spain, 28031
  • Malaga, Spain, 29010
  • Malaga, Spain, 29600
  • Murcia, Spain, 30120
  • Murcia, Spain, 30008
  • Salamanca, Spain, 37007
  • Sevilla, Spain, 41014
  • Toledo, Spain, 45004
  • Toledo, Spain, 45600
  • Valencia, Spain, 46017
  • Valencia, Spain, 46014
  • Valencia, Spain, 46010
  • Valencia, Spain, 46009
  • Valencia, Spain, 46015
  • Zaragoza, Spain, 50009
  • Asturias
    • Oviedo, Asturias, Spain, 33006
  • Barcelona
    • Manresa, Barcelona, Spain, 08240
    • Sabadell, Barcelona, Spain, 08208
  • Cadiz
    • Jerez de La Frontera, Cadiz, Spain, 11407
  • Cantabria
    • Santander, Cantabria, Spain, 39008
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20014
  • LA Coruña
    • La Coruna, LA Coruña, Spain, 15006
    • Santiago de Compostela, LA Coruña, Spain, 15706
  • Navarra
    • Pamplona, Navarra, Spain, 31008
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
  • Valencia
    • Gandia, Valencia, Spain, 46702
• Switzerland
  • Aarau, Switzerland, 5001
  • Basel, Switzerland, 4031
  • Bern, Switzerland, 3010
  • Chur, Switzerland, 7000
  • Luzern, Switzerland, 6000
  • St. Gallen, Switzerland, 9007
  • Zürich, Switzerland, 8091
• Thailand
  • Bangkok, Thailand, 10400
  • Bangkok, Thailand, 10700
  • Bangkok, Thailand, 10330
  • Khon Kaen, Thailand, 40002
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
  • Cambridge, United Kingdom, CB2 0QQ
  • Canterbury, United Kingdom, CT1 3NG
  • Cardiff, United Kingdom, CF14 4XN
  • Cottingham, United Kingdom, HU16 5JG
  • Edinburgh, United Kingdom, EH4 2XU
  • Glasgow, United Kingdom, G12 0YN
  • Leicester, United Kingdom, LE1 5WW
  • London, United Kingdom, EC1M 6BQ
  • London, United Kingdom, NW3 2QG
  • Nottingham, United Kingdom, NG5 1PB
  • Sutton, United Kingdom, SM2 5PT
• United States
  • California
    • San Diego, California, United States, 92123
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Maryland
    • Baltimore, Maryland, United States, 21215
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54311
    • Waukesha, Wisconsin, United States, 53188

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 lumpectomy alone
• Positive hepatitis serology (HBV, HCV) or positive HIV or Human T-Cell Leukemia Virus (HTLV) testing
• Patients with active infection requiring systemic treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: 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).; Other Names: RO5072759; GA101; Gazyvaro; GAZYVA®; Drug: chlorambucil; Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle
Active Comparator: 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).	Drug: chlorambucil; Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle; 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.; Other Names: Rituxan®; MabThera®
Active Comparator: 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.	Drug: chlorambucil; Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the investigator. Progressive disease required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels >20 g/L or <10 g/dL or a decrease of platelet counts >50% or <100 x 10^9/L or by a decrease of neutrophil counts >50% or <1.0 x 10^9/L).	Randomization to clinical cutoff (median observation 59.4 months)
Percentage of Participants With Progression Free Survival Events	Percentage of Participants with Progression Free Survival Events: progression, relapse, or death.	Randomization to clinical cutoff (median observation 59.4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Based on Independent Review Committee (IRC) Data	PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by Independent Review Committee. Progressive disease required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels >20 g/L or <10 g/dL or a decrease of platelet counts >50% or <100 x 10^9/L or by a decrease of neutrophil counts >50% or <1.0 x 10^9/L).	Randomization to clinical cutoff of 09 May 2013 (median observation 18.7 months)
Percentage of Participants With Progression Free Survival Events Based on Independent Review Committee (IRC) Data	Percentage of Participants with Progression Free Survival Events: progression, relapse, or death from any cause as assessed by an Independent Review Committee.	Randomization to clinical cutoff of 09 May 2013 (median observation 18.7 months)
Percentage of Participants With End of Treatment Response (EOTR)	EOTR was the first response assessment 56 days from the last dose according to the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) guidelines. Complete Response (CR) required: Peripheral blood lymphocytes below 4 x 10^9/L, Absence of significant lymphadenopathy, No hepatomegaly, No splenomegaly, Absence of disease, Blood counts above the following values (Neutrophils >1.5 x 10^9/L, Platelets >100 x 10^9/L, Hemoglobin >11g/dL) and Bone marrow at least normocellular for age. CRi was CR with incomplete bone marrow recovery. Partial Response (PR) required the following for at least 2 months from end of treatment: ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value AND Either a ≥ 50% reduction in lymphadenopathy OR ≥50% reduction of liver enlargement OR ≥50% reduction of spleen enlargement PLUS at least one of the following: Neutrophils >1.5 x 10^9/ or ≥50% increase, Platelets >100 x 10^9/L or ≥50% increase, Hemoglobin 11 g/dL or ≥50% increase.	Randomization to clinical cutoff (median observation 59.4 months)
Percentage of Participants With Best Overall Response	Best overall response according to IWCLL guidelines was defined as the percentage of patients with CR, CRi, PR or nodular Partial Response (nPR). CR required all of the following: Peripheral blood lymphocytes below 4 x 10^9/L, Absence of significant lymphadenopathy, No hepatomegaly, No splenomegaly, Absence of disease, Blood counts above the following values (Neutrophils >1.5 x 10^9/L, Platelets >100 x 10^9/L, Hemoglobin >11g/dL) and Bone marrow at least normocellular for age. CRi was CR with incomplete bone marrow recovery. PR required the following for at least 2 months from end of treatment: ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value AND Either a ≥ 50% reduction in lymphadenopathy OR ≥50% reduction of liver enlargement OR ≥50% reduction of spleen enlargement PLUS at least one of the following: Neutrophils >1.5 x 10^9/ or ≥50% increase, Platelets >100 x 10^9/L or ≥50% increase, Hemoglobin 11 g/dL or ≥50% increase.	Randomization to clinical cutoff (median observation 59.4 months)
Event Free Survival	Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy. Progressive disease as per IWCLL criteria required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels >20 g/L or <10 g/dL or a decrease of platelet counts >50% or <100 x 10^9/L or by a decrease of neutrophil counts >50% or <1.0 x 10^9/L).	Randomization to clinical cutoff (median observation 59.4 months)
Overall Survival	Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause.	Randomization to clinical cutoff (median observation 59.4 months)
Duration of Response	Duration of Response was defined as the date the response [either Complete Response (CR) or Partial Response (PR)] was first recorded until the date of Disease Progression or death due to any cause. Response was assessed according IWCLL guidelines.	Randomization to clinical cutoff (median observation 59.4 months)
Percentage of Participants With Molecular Remission at the End of Treatment	Molecular remission was defined as a minimal residual disease (MRD)-negative result at the end of treatment (assessment that occurred between 56 days and 6 months of last treatment). Molecular remission was assessed for all patients using a blood sample. Additionally, a bone marrow sample was obtained from patients whom the investigator assumed to have a complete response, consistent with the IWCLL guidelines. A combined analysis of blood and bone marrow results was conducted. A patient was considered MRD negative if result was less than 1 chronic lymphocytic leukemia (CLL) cell in 10000 leukocytes (MRD value < 0.0001) based on the method of allele specific polymerase chain reaction (ASO-PCR).	Randomization to clinical cutoff (median observation 59.4 months)
Time to Re-Treatment/New Anti-leukemic Therapy	Time to re-treatment/new anti-leukemic therapy was defined as time between the date of randomization and the date of first intake of re-treatment or new anti-leukemic therapy.	Randomization to clinical cutoff (median observation 59.4 months)
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire	The EORTC Quality of Life Questionnaire (QLQ-C30) was used to assess patient-reported outcomes (PRO) and symptom burden. The QLQ-C30 contains 30 items including the functional scales of physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items) and symptom scales including fatigue (3 items), nausea and vomiting (2 items), and pain (4 items) and six single item scales on dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be of minimally important difference to participants. A positive change from Baseline indicated improvement.	Baseline and Cycle 4 Day 1 (Cy4D1)
European Organization for Research and Treatment of Cancer (EORTC) QLQ-CLL16 Questionnaire	EORTC Quality of Life Questionnaire (QLQ-CLL16) module was used to assess patient-reported outcomes and symptom burden. The QLQ-CLL16 module includes three multi-item scales assessing fatigue (2 items), treatment side effects and disease symptoms (8 items), infection (4 items) and two single item scales on social activities and future health worries. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be of minimally important difference to participants. A positive change from Baseline indicated improvement.	Baseline and Cycle 4 Day 1 (Cy4D1)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Genentech, Inc.; German CLL Study Group

Publications and helpful links

General Publications

• Dimier N, Delmar P, Ward C, Morariu-Zamfir R, Fingerle-Rowson G, Bahlo J, Fischer K, Eichhorst B, Goede V, van Dongen JJM, Ritgen M, Bottcher S, Langerak AW, Kneba M, Hallek M. A model for predicting effect of treatment on progression-free survival using MRD as a surrogate end point in CLL. Blood. 2018 Mar 1;131(9):955-962. doi: 10.1182/blood-2017-06-792333. Epub 2017 Dec 18.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2009
• Primary Completion (Actual): August 31, 2013
• Study Completion (Actual): August 23, 2017

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (Estimate): February 3, 2014

Study Record Updates

• Last Update Posted (Actual): September 14, 2018
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Rituximab; Obinutuzumab; Chlorambucil
• Other Study ID Numbers: BO21004 (Stage 2); 2009-012476-28; CLL1