Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01287741
Recruitment Status : Terminated (The study was closed by the Sponsor according to the protocol-specified minimum post-treatment follow-up period of 3 years.)
First Posted : February 1, 2011
Results First Posted : August 17, 2017
Last Update Posted : April 12, 2019
Sponsor:
Collaborator:
Fondazione Italiana Linfomi ONLUS
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 31, 2011
First Posted Date  ICMJE February 1, 2011
Results First Submitted Date  ICMJE April 7, 2017
Results First Posted Date  ICMJE August 17, 2017
Last Update Posted Date April 12, 2019
Actual Study Start Date  ICMJE July 26, 2011
Actual Primary Completion Date April 29, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2019)
Median Time to Progression-Free Survival (PFS), Investigator-Assessed [ Time Frame: Baseline up to approximately 6.5 years (up to 31 January 2018) ]
Kaplan Meier estimate of the median PFS was defined as the time at which half of the participants have progressed (progressive disease [PD]). Progression-free survival was defined as the time from randomization until the first documented day of disease progression or relapse, using a modified version of the Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on the basis of investigator assessments. 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).
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2011)
Progression-Free Survival, Assessed by the Investigator According to a Modified Version of the Revised Response Criteria for Malignant Lymphoma [ Time Frame: up to approximately 78 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2019)
  • Median Time to Progression-Free Survival (PFS), Independent Review Committee (IRC)-Assessed [ Time Frame: Baseline up to approximately 4 years and 9 months (up to 29 April 2016) ]
    Kaplan Meier estimate of median PFS was defined as time at which half of participants have progressed (progressive disease [PD]). Progression-free survival was defined as time from randomization until first documented day of disease progression or relapse, using a modified version of Revised Response Criteria for Malignant Lymphoma, or death from any cause, whichever occurred first, on basis of IRC assessments. Progression was defined as at least 50% increase in nodal lesions or >/=50% increase in any node > 1 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 diameter </= 1 cm such that it is now >1.5 cm. Tumor measurements were obtained by CT or MRI. This outcome measure used data from primary analysis which included all 1418 participants.
  • Median Time to Overall Survival (OS) [ Time Frame: Baseline up to approximately 6.5 years (up to 31 January 2018) ]
    Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death. 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.
  • Overall Response Rate (ORR), Investigator-Assessed [ Time Frame: Baseline up to approximately 6.5 years (up to 31 January 2018) ]
    Overall response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.
  • Overall Response Rate (ORR), IRC-Assessed [ Time Frame: Baseline up to approximately 4 years and 9 months (up to 29 April 2016) ]
    Overall response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Overall response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites. This outcome measure used data from primary analysis which included all 1418 participants.
  • Complete Response (CR) at the End of Treatment, Investigator-Assessed [ Time Frame: Baseline up to approximately 6.5 years (up to 31 January 2018) ]
    Percentage of participants with complete response was determined on the basis of investigator assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease.
  • Complete Response (CR) at the End of Treatment, IRC-Assessed [ Time Frame: Baseline up to approximately 4 years and 9 months (up to 29 April 2016) ]
    Percentage of participants with complete response was determined on the basis of IRC assessments according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma, 2007. Tumor assessments were performed with CT/MRI with or without PET. Complete response was defined as the disappearance of all evidence of disease. This outcome measure used data from primary analysis which included all 1418 participants.
  • Median Time to Event-Free Survival (EFS), Investigator-Assessed [ Time Frame: Baseline up to death or disease progression, or initiation of new anti-lymphoma treatment (NALT), whichever occurred first, approximately 6.5 years (up to 31 January 2018) ]
    Kaplan Meier estimate of median EFS is the time at which half of the participants have progressed. Event-free survival was defined as the time from the date of randomization until the date of disease progression, relapse, initiation of a new non-protocol-specified anti-lymphoma treatment, or death from any cause on the basis of investigator 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.
  • Median Time to Disease-Free Survival (DFS), Investigator-Assessed [ Time Frame: Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018) ]
    Kaplan Meier estimate of median DFS was defined as time at which half of participants have disease progression/relapse or death from any cause. Disease-free survival was defined as time from date of the first occurrence of a documented CR to date of disease progression/relapse or death from any cause on basis of investigator assessments with 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.
  • Duration of Response (DOR), Investigator-Assessed [ Time Frame: Baseline up to death or disease progression, whichever occurred first, approximately 6.5 years (up to 31 January 2018) ]
    DOR: time from first occurrence of documented CR or PR to disease progression/relapse, or death from any cause for participants with a response of CR or PR. Tumor assessments were performed with CT/MRI. CR: disappearance of all target lesions. PR: >/=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 nodule regression >/= 50%. Progression/relapse: at least 50% increase in nodal lesions or >/=50% increase in any node > 1 cm or >/= 50% increase in other target lesions (e.g., splenic or hepatic nodules) and/or any new bone marrow involvement and/or 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. A participant in the Rituximab+CHOP arm with the longest follow-up, 53 months, had an event. The criterion for median was the minimum time when survival went below 50%.
  • Time to Next Anti-Lymphoma Treatment (TTNALT) [ Time Frame: Baseline up to start of next anti-lymphoma treatment or death due to any cause, whichever occurred first, approximately 6.5 years (31 January 2018) ]
    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.
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to approximately 6.5 years (up to 31 January 2018) ]
    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.
  • Percentage of Participants With Human Anti-Human Antibodies (HAHAs) to Obinutuzumab [ Time Frame: Pre-dose (Hour 0) on Cycle (C) 4 Day (D) 1, at end of treatment/early termination (up to Month 6), every 6 months thereafter for 30 months (cycle length = 21 days) ]
    The presence of HAHAs to obinutuzumab was assessed in the first 100 randomized participants.
  • Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale Score [ Time Frame: Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to approximately 6.5 years, (cycle length = 21 days) ]
    The FACT-Lym subscale was developed to assess health-related quality of life in participants with non-Hodgkin lymphoma. The score range is 0-60, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement.
  • Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) Domain Scores [ Time Frame: Baseline (pre-dose [Hour 0] on C1D1), C3D1, end of treatment (up to Month 6), every 12 months thereafter up to data cut-off, up to approximately 6.5 years, (cycle length = 21 days) ]
    The EORTC QLQ-C30 is a health-related quality of life questionnaire. A higher score indicates better quality of life, with changes of 5 to 10 points considered to be a minimally important difference to participants.
  • Serum Concentrations of Obinutuzumab in Japanese Participants With Diffuse Large B-Cell Lymphoma (DLBCL) [ Time Frame: C1: D1 post-infusion and 20-28 and 66-80 hours after end of infusion, D8 and D15 pre-and post-infusion; C2: D1 pre- and post-infusion; C4: D1 pre- and post-infusion; C6: D1 pre- and post-infusion; C8: D1 pre- and post-infusion (cycle length = 21 days) ]
    Serum samples for assessment of obinutuzumab serum concentrations were collected only from a subset of Japanese participants following administration of 1000 mg obinutuzumab.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2011)
  • Overall Survival [ Time Frame: up to approximately 78 months ]
  • Overall response rate at the end of treatment, assessed by the investigator and the Independent Review Committee (IRC) [ Time Frame: 24 weeks ]
  • Complete response rate at the end of treatment, assessed by investigator and IRC [ Time Frame: 24 weeks ]
  • Progression-free survival assessed by the Independent Review Committee [ Time Frame: up to approximately 78 months ]
  • Event-free survival, defined as time to progression or relapse, or initiation of non-protocol-specified anti-lymphoma therapy, or death, whichever occurs first [ Time Frame: up to approximately 78 months ]
  • Disease-free survival, assessed by investigator [ Time Frame: up to approximately 78 months ]
  • Duration of response, assessed by the investigator [ Time Frame: up to approximately 78 months ]
  • Time to next lymphoma treatment [ Time Frame: up to approximately 78 months ]
  • Safety: Incidence of adverse events [ Time Frame: up to approximately 78 months ]
  • Quality of life (Functional Assessment of Cancer Therapy-Lymphoma subscale, Euro-Quality of Life 5D questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Core 30) [ Time Frame: up to approximately 78 months ]
  • Medical resource utilization (hospitalizations, drug therapies, medical and surgical procedures and treatments) [ Time Frame: up to approximately 78 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)
Official Title  ICMJE A Phase III, Multicenter, Open-Label Randomized Trial Comparing the Efficacy of GA101 (RO5072759) in Combination With CHOP (G-CHOP) Versus Rituximab and CHOP (R-CHOP) in Previously Untreated Patients With CD20-Positive Diffuse Large B-Cell Lymphoma (DLBCL)
Brief Summary This open-label, randomized, parallel group study will evaluate the efficacy and safety of obinutuzumab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone or prednisone (CHOP) chemotherapy versus rituximab (MabThera/Rituxan) with CHOP in previously untreated participants with cluster of differentiation 20 (CD20)-positive diffuse large B-cell lymphoma (DLBCL). Participants will be randomized to receive either obinutuzumab 1000 milligrams (mg) intravenously (IV) every 21 days or rituximab 375 milligrams per square meter (mg/m^2) IV every 21 days for 8 cycles, in addition to 6-8 cycles of CHOP chemotherapy IV every 21 days. Participants randomized to the obinutuzumab arm will receive an additional two doses on Days 8 and 15 of Cycle 1. Anticipated time on study treatment is 24 weeks.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-Cell Lymphoma
Intervention  ICMJE
  • Drug: Rituximab
    Rituximab at a dose of 375 mg/m^2, administered by intravenous (IV) infusion on Day 1 of each 21-day cycle for 8 cycles.
    Other Name: MabThera, Rituxan
  • Drug: Obinutuzumab
    Obinutuzumab 1000 mg IV infusion, administered on Day 1 of each 21-day cycle for 8 cycles. During Cycle 1, obinutuzumab was also infused on Days 8 and 15.
    Other Name: GA101, RO5072759
  • Drug: Cyclophosphamide
    Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle.
  • Drug: Doxorubicin
    Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle.
  • Drug: Vincristine
    Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle.
  • Drug: Prednisone
    Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle.
Study Arms  ICMJE
  • Active Comparator: Rituximab+Chemotherapy
    Participants received eight 21-day cycles of rituximab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
    Interventions:
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone
  • Experimental: Obinutuzumab+Chemotherapy
    Participants received eight 21-day cycles of obinutuzumab, combined with six or eight cycles of standard cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) chemotherapy (21-day cycles). Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1. Prior to study start, study centers chose whether they planned to administer 6 or 8 cycles of CHOP chemotherapy.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 4, 2014)
1418
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2011)
1400
Actual Study Completion Date  ICMJE January 31, 2018
Actual Primary Completion Date April 29, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Previously untreated CD20-positive DLBCL
  • At least 1 bi-dimensionally measurable lesion (greater than [>]1.5 centimeters [cm] in its largest dimension on the computed tomography [CT] scan)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  • Adequate hematological function
  • Low-intermediate, high-intermediate or high-risk International Prognostic Index (IPI) score (low-risk IPI score: IPI 1 irrespective of bulky disease or IPI 0 with bulky disease, defined as one lesion greater than equal to (>/=) 7.5 cm)
  • Left ventricular ejection fraction (LVEF) >/=50 percent (%) on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram

Exclusion Criteria:

  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products or to any component of CHOP or obinutuzumab
  • Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
  • Participants with transformed lymphoma and participants with follicular lymphoma IIIB
  • Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation
  • Prior treatment with cytotoxic drugs or rituximab for another condition (for example, rheumatoid arthritis) or prior use of an anti-CD20 antibody
  • Prior use of any monoclonal antibody within 3 months of the start of Cycle 1
  • Corticosteroid use of >30 milligrams per day (mg/day) of prednisone or equivalent, for purposes other than lymphoma symptom control
  • Primary central nervous system (CNS) lymphoma and secondary CNS involvement by lymphoma, mantle-cell lymphoma (MCL), or histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, plasmablastic lymphoma, and primary cutaneous DLBCL
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Brazil,   Canada,   China,   Colombia,   Czechia,   Denmark,   Germany,   Hong Kong,   Hungary,   Italy,   Japan,   Korea, Republic of,   Mexico,   Panama,   Peru,   Poland,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Switzerland,   Taiwan,   Thailand,   United Kingdom,   United States
Removed Location Countries Czech Republic,   India
 
Administrative Information
NCT Number  ICMJE NCT01287741
Other Study ID Numbers  ICMJE BO21005
2010-024194-39
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Fondazione Italiana Linfomi ONLUS
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP