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A Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM)

Primary Purpose

Non-Hodgkin's Lymphoma

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Obinutuzumab

Cyclophosphamide

Doxorubicin

Vincristine

Prednisone

Bendamustine

Rituximab

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Cluster of differentiation 20 (CD20)-positive indolent B-cell non-Hodgkin's lymphoma (follicular lymphoma or splenic, nodal or extranodal marginal zone lymphoma)
Stage III or IV disease, or Stage II bulky disease (defined as tumor diameter greater than or equal to [>/=] 7 centimeters [cm])
For participants with follicular lymphoma: requirement for treatment according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
For participants with symptomatic splenic, nodal, or non-gastric extranodal marginal zone lymphoma: disease that is de novo or has relapsed following local therapy (i.e. surgery or radiotherapy) and requires therapy as assessed by the investigator
At least one bi-dimensionally measurable lesion (greater than [>] 2 cm in its largest dimension by computed tomography [CT] scan or magnetic resonance imaging [MRI])
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Adequate hematologic function

Exclusion Criteria:

Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's macroglobulinaemia
Ann Arbor Stage I disease
History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
Known hypersensitivity to any of the study drugs or sensitivity to murine products, or history of sensitivity to mannitol
For participants with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma with chemotherapy, immunotherapy, or radiotherapy
For participants with non-follicular lymphoma: prior treatment with chemotherapy or immunotherapy
Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle 1
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
For participants who will be receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP): left ventricular ejection fraction (LVEF) less than (<) 50% by multiple-gated acquisition (MUGA) scan or echocardiogram
History of prior other malignancy with the exception of curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study
Known active infection, or major episode of infection within 4 week prior to the start of Cycle 1
Vaccination with a live vaccine within 28 days prior to randomization
Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for diagnosis
Abnormal laboratory values as defined by protocol for creatinine, creatinine clearance, aspartate transaminase (AST) or alanine transaminase (ALT), total bilirubin, international normalized ration (INR), partial thromboplastin time (PTT) or activated partial thromboplastin time (aPPT), unless these abnormalities are due to underlying lymphoma
Positive test results for human immunodeficiency virus (HIV), human T-lymphotropic virus 1 (HTLV1), hepatitis C or chronic hepatitis B
Pregnant or lactating women
Life expectancy <12 months
Participation in another clinical trial with drug intervention within 28 days prior to start of Cycle 1 and during study

Sites / Locations

Highlands Oncology Group
The Regents of the University of California; Office of Research
Kootenai Cancer Center
Illinois Cancer Care, P.C. - Galesburg
Siouxland Hematology/Oncology
University of Kansas; Medical Center & Medical pavilion
Cancer Center of Kansas
Mercy Medical Research Institute
MT Cancer Inst Fndtn; MT Can Spec
San Juan Oncology Associates
Providence St. Vincent Medical Center
Northwest Medical Specialties
Concord Repatriation General Hospital; Haematology
Westmead Hospital; Haematology
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
St Vincent'S Hospital; Haematology
Peter MacCallum Cancer Centre; Department of Haematology
Austin and Repatriation Medical Centre; Cancer Services
Monash Medical Centre; Haematology
Fiona Stanley Hospital
UZ Gent
AZ Groeninge
UZ Leuven Gasthuisberg
Tom Baker Cancer Centre-Calgary
Cross Cancer Institute
Dr. Georges L. Dumont University Hospital Centre
Ottawa General Hospital
North York General Hospital
Humber River Hospital
Toronto East General Hospital; Haematology/Oncology
Hopital Charles Lemoyne; Centre Integre de Lutte Contre Le Cancer de La Monteregie
Peking University First Hospital
Cancer Hospital Chinese Academy of Medical Sciences.
Beijing Cancer Hospital
General Hospital of Chinese PLA; Department of Hematology
the First Hospital of Jilin University
Fujian Medical University Union Hospital
Sun Yet-sen University Cancer Center
Harbin Medical University Cancer Hospital
Jiangsu Cancer Hospital
Jiangsu Province Hospital
Fudan University Shanghai Cancer Center
Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Fn Hr. Kralove; IV. Interni Hematologicka Klinika
Vseobecna Fakultni Nemocnice v Praze, I. Interni Klinika - Klinika Hematoonkologie VFN a 1. LF UK
Helsinki University Central Hospital; Dept of Oncology
Hotel Dieu; Medecine D
Hopital Augustin Morvan; Hematologie
Chu Estaing; Hematologie Clinique Adultes
Clinique Victor Hugo
Hopital De La Conception; Hematologie Clinique
Hopital Saint Eloi; Hematologie Oncologie Medicale
Hopital Saint Jean; Hematologie
Onkologischer Schwerpunkt am Oskar-Helene-Heim; Dres. Herrenberger, Keitel-Wittig u. Kirsch
Klinikum Chemnitz gGmbH Krankenhaus Küchwald Klinik f.Innere Medizin III
Städtisches Klinikum Dessau
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex; Fachaerzte fuer Innere Medizin
HELIOS Klinikum Erfurt I.Medizinische Klinik
St.-Antonius-Hospital gGmbH; Klinik für Hämatologie und Onkologie
Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung
Klinik Johann Wolfgang von Goethe Uni; Medizinische Klinik II
Universitätsklinikum Freiburg; Klinik für Innere Medizin I; Hämatologie/Onkologie
Universitätsklinikum Greifswald Klinik für Innere Medizin C und Poliklinik
Uni Göttingen, Georg-August-Universität; Klinik für Hämatologie und Medizinische Onkologie
Kath. Krankenhaus Hagen gem. GmbH, St.-Josefs-Hospital; Klinik für Hämatologie und Onkologie
Onkologische Schwerpunktpraxis Dres. Bernd Gaede, Hans-Ulrich Ehlers, Ulrike Rodewig u.w.
Dres.Andreas Karcher und Stefan Fuxius
Uniklinik Heidelberg, Medizinische Klinik & Poliklinik V
Universitaetsklinikum des Saarlandes; medizinische Klinik und Poliklinik; Innere Medizin I
Universitätsklinikum Jena; Klinik für Innere Medizin II
UKSH, Campus Kiel; Klinik für Innere Medizin II, Hämatologie und Internistische Onkologie
Institut für Versorgungsforschung in der Onkologie GbR Koblenz
Klinik der Uni zu Köln; Klinik für Innere Medizin
Tagesklinik Landshut; Hämatologie/Onkologie
Gemeinschaftspraxis für Hämatologie und Onkologie
Klinikum St.Georg gGmbH Klinik für Internistische Onkologie und Hämotologie
Klinikum der Stadt Ludwigshafen; Medizinische Klinik A
Onkologische Gemeinschaftspraxis
Otto von Guericke Uni Magdeburg Uniklinik; Hämatologie/Onkologie
Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik
Mannheimer Onkologie Praxis Dres. Jürgen Brust Dieter Schuster
Klinikum Mannheim III. Medizinische Klinik
Kliniken Ostalb, Stauferklinikum Schwäbisch-Gmünd; Zentrum für Innere Medizin
St. Frankziskus Krankenhaus, Med. Klinik I; Klinik für Hämatologie,Onkologie u. Gastroenterologie
Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III
Klinikum rechts der Isar der TU München; III. Medizinischen Klinik (Hämatologie/Onkologie)
Gemeinschaftspraxis Dr. med. Holger Klaproth
Pius-Hospital; Klinik fuer Haematologie und Onkologie
Brüderkrankenhaus St. Josef
Prosper-Hospital, Medizinische Klinik I
Krankenhaus Barmherziger Brüder; Klinik für Internistische Onkologie / Hämatologie
Praxis für Hämatologie & Onkologie
Krankenhaus der Barmherzigen Brüder Trier; Innere Medizin I, Hämatologie / Internistische Onkologie
Universität Tübingen; Med. Klinik; Innere Medizin I
Universtitätsklinikum Ulm; Klinik für Innere Medizin III
Helios Dr. Horst Schmidt Kliniken; Klinik Innere MED III: Hämatologie, Onkologie, Palliativmedizin
Hämatologisch-Onkologische Schwerpunktpraxis Dres. Schlag & Schöttker
Semmelweis University, First Dept of Medicine
National Institute of Oncology, A Dept of Internal Medicine
University of Debrecen Medical and Health Science Center, Institute of Internal Medicine, Hematology
Petz Aladar Megyei Korhaz; Hematologia
University of Szeged, II Dept of Internal Medicine
Rambam Medical Center; Heamatology & Bone Marrow Transplantation
Beilinson Medical Center; Haematology
Chaim Sheba Medical Center; Hematology BMT & CBB
Azienda Ospedaliera Universitaria di Modena
Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
ASST PAPA GIOVANNI XXIII; Ematologia
Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
A.O. Univ.Ospedali Riuniti Umerto I -G.M.Lancisi G.Salesi; U.O. Clinica Di Ematologia
Ospedale V. Cervello; U.O. Ematologia E Trapianti
Uni Degli Studi; Dip.Med.Clinica E Sperim. Ematologia
Aichi Cancer Center Hospital; Hematology and Cell Therapy
Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital; Hematology & Oncology
Nagoya City University Hospital; Hematology and Oncology
Aomori Prefectural Central Hospital; Hematology
Chiba Cancer Center;Hematology and Oncology
National Cancer Center Hospital East;Hematology
Shikoku Cancer Center; Hematology and Oncology
National Hospital Organization Kyushu Cancer Center; Hematology
Gunma University Hospital;Hematology
Hiroshima University Hospital; Hematology
Kobe City Medical Center General Hospital; Hematology
Hyogo Cancer Center; Department of hematology
Tokai University Hospital; Hematology
Kumamoto University Hospital; Hematology Rheumatology and Clinical Immunology
University Hospital, Kyoto Prefectural University of Medicine; Hematology
Tohoku University Hospital; Hematology and Immunology
Shinshu University Hospital; Hematology
Niigata Cancer Center Hospital; Internal Medicine
Matsushita Memorial Hospital; hematology
Jichi Medical University Hospital; Hematology
National Cancer Center Hospital; Hematology
Toranomon Hospital; Hematology
The Cancer Institute Hospital of JFCR; Hematology Oncology
The Jikei University Daisan Hospital; Department of Clinical Oncology and Hematology
FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
Regional Clinical Hospital N.A. Semashko; Hematology
Republican Clinical Hospital n.a. Baranov; Haematology
Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
Corporacio Sanitaria Parc Tauli; Servicio de Hematologia
Fundacion Hospital de Alcorcon; Servicio de Hematologia
Hospital de Basurto; Servicio de Hematologia
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Hospital Universitario la Paz; Servicio de Hematologia
Sahlgrenska Universitetssjukhuset; Sektionen för hematologi och koagulation
Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
National Taiwan Universtiy Hospital; Division of Hematology
Chang Gung Medical Foundation - Linkou; Division of Hematology- Oncology
Aberdeen Royal Infirmary; Haematology - Ward 16
Queen Elizabeth Hospital; Centre for Clinical Haematology
Royal Bournemouth General Hospital; Haematology
Bristol Haematology and Oncology Centre
Addenbrookes Hospital; Haematology
Kent & Canterbury Hospital; Clinical Haematology
Velindre NHS Trust; Haematology Department
Castle Hill Hospital; The Queens Centre for Oncology and Haematology
Western General Hospital; Department of Haematology
Beatson West of Scotland Cancer Centre
James Paget Hospital; Haematology Department
Princess Alexandra Hospital; Department of Haematology
St James Uni Hospital; Icrf Cancer Medicine Research Unit
Leicester Royal Infirmary; Dept of Haematology
St Bartholomew's Hospital
King'S College Hospital; Haematology
St. George'S Hospital; Haematology
Hammersmith Hospital; Haematology
University College Hospital; Macmillan Cancer Centre
Christie Hospital; Breast Cancer Research Office
Norfolk & Norwich Hospital; Dept of Haematology
Nottingham City Hospital; Dept of Haematology
Churchill Hospital; Oxford Cancer and Haematology Centre
Queen Alexandra Hospital; Haematology and Oncology Centre
Southampton General Hospital; Medical Oncology
Royal Marsden Hospital; Dept of Medical Oncology
Singleton Hospital; Pharmacy
Great Western;Department of Haematology
Royal Cornwall Hospital; Haematology Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Rituximab+Chemotherapy

Obinutuzumab+Chemotherapy

Arm Description

Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.

Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.

Outcomes

Primary Outcome Measures

Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed

Progression-free survival in participants with follicular lymphoma was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by computed tomography (CT) or magnetic resonance imaging (MRI).

Secondary Outcome Measures

Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed

Progression-Free Survival in the Overall Study Population, Investigator-Assessed

Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.

Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed

Progression-free survival in the participants with follicular lymphoma was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. In the first 170 patients with follicular lymphoma, an FDG-PET was mandatory where a PET scanner was available.

Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC)

Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.

Overall Response (Follicular Lymphoma Population), Investigator-Assessed

Overall response in the follicular lymphoma population was defined as percentage of participants with PR or complete response CR determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with and without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR.

Overall Response (Overall Study Population), Investigator-Assessed

Overall response in the overall study population was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without positron emission tomography (PET). CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR.

Complete Response (Follicular Lymphoma Population), Investigator-Assessed

Percentage of participants with complete response in the follicular lymphoma population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.

Complete Response (Overall Study Population), Investigator-Assessed

Percentage of participants with complete response in the overall study population was determined on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.

Overall Response (Follicular Lymphoma Population), IRC-Assessed

Overall response in the follicular lymphoma population was defined as percentage of participants with PR or complete response CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Overall Response (OR) = CR + PR.

Overall Response (Overall Study Population), IRC-Assessed

Overall response in the overall study population was defined as percentage of participants with PR or CR determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions; PR was defined as >=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%; Overall Response (OR) = CR + PR.

Complete Response (Follicular Lymphoma Population), IRC-Assessed

Percentage of participants with complete response in the follicular lymphoma population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.

Complete Response (Overall Study Population), IRC-Assessed

Percentage of participants with complete response in the overall study population was determined on the basis of IRC assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI with or without PET. CR was defined as disappearance of all target lesions.

Overall Survival (Follicular Lymphoma Population)

Overall survival in the follicular lymphoma population was defined as the time from the date of randomization to the date of death from any cause. Reported is the percentage of participants with event.

Overall Survival (Overall Study Population)

Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. Reported is the percentage of participants with event.

Event-Free Survival (Follicular Lymphoma Population)

Event-free survival in the follicular lymphoma population was defined as the time from the date of randomization to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. Reported is the percentage of participants with an event.

Event-Free Survival (Overall Study Population)

Event-free survival in the overall study population was defined as the time from the date of randomization to the date to disease progression/relapse, death from any cause, or initiation of a new anti-lymphoma treatment (NALT) on the basis of investigator assessment assessments with the use of Revised Response Criteria for Malignant Lymphoma. Disease progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI. Reported is the percentage of participants with event.

Disease-Free Survival (Follicular Lymphoma Population)

Disease-free survival in the follicular lymphoma population was defined as the time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause for the subgroup of participants with a response of CR at any time prior to NALT on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma (RRCML). Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Reported is the percentage of participants with event.

Disease-Free Survival (Overall Study Population)

Disease-free survival in the overall study population was defined as the time from the date of the first occurrence of a documented CR to the date of disease progression/ relapse, or death from any cause for the subgroup of participants with a response of CR at any time prior to NALT on the basis of investigator assessments with the use of Revised Response Criteria for Malignant Lymphoma. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Reported is the percentage of participants with event.

Duration of Response (DOR) (Follicular Lymphoma Population), Investigator-Assessed

DOR was defined as the time from first occurrence of a documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR any time prior to NALT based on RRCML. Tumor assessments were performed with CT/MRI. CR was defined as disappearance of all target lesions. PR was defined as >/=50% decrease target lesions in up to six dominant lesions identified at baseline, no new lesions and no increase in the size of the liver, spleen, or other nodes. Splenic and hepatic nodules must have regressed by >/= 50%. Progression/relapse was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm.

Duration of Response (DOR) (Overall Study Population), Investigator-Assessed

Time to Next Anti-Lymphoma Treatment (Follicular Lymphoma Population)

Time to next anti-lymphoma treatment was defined as the time from the date of randomization to the start date of the next anti-lymphoma treatment or death from any cause. Reported is the percentage of participants with event.

Time to Next Anti-Lymphoma Treatment (Overall Study Population)

Percentage of Participants With Adverse Events

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Change From Baseline in All Domains of FACT-G (Follicular Lymphoma Population)

FACT-G consists of the following 4 FACT-Lym sub-questionnaires: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24) and Functional Well-being (range: 0-28). Higher scores indicate better outcomes. A positive change from baseline indicates improvement. Maint = Maintenance period.

Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population)

The FACT-Lym TOI Score for the follicular lymphoma population was derived from the following 3 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym TOI Score is the sum of the 3 individual subscales (range 0-116). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.

Change From Baseline in FACT-Lym Individual Subscale Lymphoma Score (Follicular Population)

The FACT-Lym Individual Subscale Lymphoma Score for the follicular lymphoma population was derived from the Lymphoma subscale questionnaire (range: 0-60). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.

Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score (Follicular Population)

The FACT-Lym Total Score for the follicular lymphoma population was derived from the following 5 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Social/Family Well-being (range: 0-28), Emotional Well-being (range: 0-24),Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym Total Score is the sum of all 5 individual subscales (range 0-168). Higher scores indicate better outcomes. A positive change from baseline indicates an improvement.

Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Induction Phase

The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1. Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Completion (Compl) includes completion visit and early termination visit. Maintenance/Observation is indicated as Maint/Obs.

Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Maintenance/Observation Phase

The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1 Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Maintenance/Observation is indicated as Maint/Obs. Completion includes completion visit and early termination visit.

Change From Baseline in Euro-Quality of Life-5 Dimensions (EQ-5D) Questionnaire Summary Score (Follicular Lymphoma Population) During Follow Up Phase

The EQ-5D is a quality of life questionnaire with five questions, each with three categories (no problem, moderate problem, severe problems) and a visual analogue scale (VAS) from 0 (worst possible health state) to 100 (best possible health state. Summary score ranges from 0 to 1. Higher scores indicate better outcomes. A positive change from baseline indicates an improvement. Maintenance/Observation is indicated as Maint/Obs in data categories. Completion includes completion visit and early termination visit.

Full Information

NCT ID

NCT01332968

First Posted

April 8, 2011

Last Updated

August 9, 2022

Sponsor

Hoffmann-La Roche

Collaborators

German Low Grade Lymphoma Study Group, Institute of Cancer Research, United Kingdom

1. Study Identification

Unique Protocol Identification Number

NCT01332968

Brief Title

A Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM)

Official Title

A Multicenter, Phase III, Open-Label, Randomized Study in Previously Untreated Patients With Advanced Indolent Non-Hodgkin's Lymphoma Evaluating the Benefit of GA101 (RO5072759) Plus Chemotherapy Compared With Rituximab Plus Chemotherapy Followed by GA101 or Rituximab Maintenance Therapy in Responders

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

July 6, 2011 (Actual)

Primary Completion Date

February 1, 2016 (Actual)

Study Completion Date

July 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

Collaborators

German Low Grade Lymphoma Study Group, Institute of Cancer Research, United Kingdom

4. Oversight

5. Study Description

Brief Summary

This open-label, randomized study will assess the efficacy and safety of obinutuzumab (RO5072759) in combination with chemotherapy compared to rituximab (MabThera/Rituxan) with chemotherapy followed by obinutuzumab or rituximab maintenance in participants with untreated advanced indolent non-Hodgkin's lymphoma. After the end of the induction period, participants achieving response (Complete response [CR] or partial response [PR]) will undergo a maintenance period continuing on the randomized antibody treatment alone every 2 months until disease progression for a total of 2 years. Anticipated time on study treatment is up to approximately 2.5 years. After maintenance or observation, participants will be followed for 5 years until progression. After progression, participants will be followed for new anti-lymphoma therapy and overall survival until the end of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-Hodgkin's Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1401 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Rituximab+Chemotherapy

Arm Type

Active Comparator

Arm Description

Arm Title

Obinutuzumab+Chemotherapy

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Obinutuzumab

Other Intervention Name(s)

GA101; RO5072759

Intervention Description

Obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion will be administered on Day 1, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent cycle during induction period and obinutuzumab 1000 mg IV infusion every 2 months during maintenance period.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

Cyclophosphamide 750 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

Doxorubicin 50 mg/m^2 IV will be administered on Day 1 of each cycle during induction period.

Intervention Type

Drug

Intervention Name(s)

Vincristine

Intervention Description

Vincristine 1.4 mg/m^2 (maximum 2 mg) IV will be administered on Day 1 of each cycle during induction period.

Intervention Type

Drug

Intervention Name(s)

Prednisone

Intervention Description

Prednisone 100 mg (or equivalent prednisolone or methylprednisolone) will be administered orally on Days 1-5 of each cycle during induction period.

Intervention Type

Drug

Intervention Name(s)

Bendamustine

Intervention Description

Bendamustine 90 mg/m^2 IV infusion will be administered on Days 1 and 2 of each cycle during induction period.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

MabThera/Rituxan

Intervention Description

Rituximab 375 milligrams per square meter (mg/m^2) IV infusion will be administered on Day 1 of each cycle during induction period and rituximab 375 mg/m^2 every 2 months during maintenance period.

Primary Outcome Measure Information:

Title

Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed

Description

Time Frame

Baseline up to data cut-off (up to approximately 4 years and 7 months)

Secondary Outcome Measure Information:

Title

Progression-Free Survival in the Follicular Lymphoma Population, Investigator-Assessed

Description

Time Frame

Baseline up to final analysis (up to 10 years)

Title

Progression-Free Survival in the Overall Study Population, Investigator-Assessed

Description

Time Frame

Baseline up to data cut-off (up to approximately 5 years and 2 months)

Title

Progression-Free Survival (Follicular Lymphoma Population), IRC-Assessed

Description

Time Frame

Baseline up to data cut-off (up to approximately 5 years and 2 months)

Title

Progression-Free Survival (Overall Study Population), Assessed by Independent Review Committee (IRC)

Description

Progression-free survival in the overall study population was defined as the time from randomization until the first documented day of disease progression or death from any cause, whichever occurred first, on the basis of IRC assessments according to the Revised Response Criteria for Malignant Lymphoma. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 centimeter (cm) or >/= 50% increase in other target measurable lesions (e.g., splenic or hepatic nodules) and/or appearance of any new bone marrow involvement and/or appearance of any new lesion > 1.5 cm or >/= 50% increase in any previously involved node with a diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT/MRI.

Time Frame

Baseline up to data cut-off (up to approximately 5 years and 2 months)

Title

Overall Response (Follicular Lymphoma Population), Investigator-Assessed

Description

Time Frame