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NCT01414855

A Study of Obinutuzumab [RO5072759 (GA101)] in Combination With CHOP Chemotherapy in Patients With Previously Untreated Advanced Diffuse Large B-Cell Lymphoma (GATHER)

Completed Phase 2 Results posted Last updated 25 April 2018
What this trial tests

Phase 2 trial testing obinutuzumab in Lymphoma, B-Cell in 100 participants. Completed in 23 December 2016.

Timeline
31 August 2011
Primary endpoint
31 December 2013
23 December 2016

Quick facts

Lead sponsorGenentech, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment100
Start date31 August 2011
Primary completion31 December 2013
Estimated completion23 December 2016
Sites38 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Genentech, Inc. — full company profile →

Who can join

18 and older, any sex, with Lymphoma, B-Cell. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment Primary · From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

Complete response rate is defined as the percentage of participants with Complete Response (CR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the investigator using regular clinical and laboratory examinations, fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT). CR is the disappearance of all evidence of disease.

GroupValue95% CI
Obinutuzumab + CHOP55.044.73 – 64.97
Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment Primary · From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

Overall response rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the investigator using regular clinical and laboratory examinations, FDG-PET and computed tomography (CT). CR is the disappearance of all evidence of disease. PR is at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites.

GroupValue95% CI
Obinutuzumab + CHOP82.073.05 – 88.97
Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment Secondary · From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

Complete response rate is defined as the percentage of participants with Complete Response (CR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the IRF using CT scans, PET scans and pertinent clinical information. CR is the disappearance of all evidence of disease.

GroupValue95% CI
Obinutuzumab + CHOP58.047.71 – 67.80
Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment Secondary · From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

Overall response rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al., 2007). Disease response was evaluated by the IRF using CT scans, PET scans and pertinent clinical information. CR is the disappearance of all evidence of disease. PR is at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites.

GroupValue95% CI
Obinutuzumab + CHOP75.065.34 – 83.12
Progression-Free Survival (PFS) as Assessed by the Investigator Secondary · From the first dose of study treatment to PFS assessment (up to 64 months)

PFS was defined as the time from the date of the first dose of study treatment until the date of disease progression, relapse, or death from any cause.

GroupValue95% CI
Obinutuzumab + CHOP48.346.1 – 58.2
Duration of Response (DOR) Secondary · From the response assessment to relapse, progression, or death (up to 64 months)

DOR is defined as first occurrence of documented response (CR or PR) until the first occurrence of relapse or progression or death of any cause. CR: disappearance of all evidence of disease. PR: at least 50% regression of measurable disease compared to tumors measured by a baseline scan and no new sites.

GroupValue95% CI
Obinutuzumab + CHOP45.643.1 – 55.7
Percentage of Participants With Adverse Events as a Measure of Safety Secondary · From the first dose of study treatment to end of study (up to 5 years 4 months)

An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug or other protocol-imposed intervention. Preexisting conditions that worsened during the study were reported as adverse events.

GroupValue95% CI
Obinutuzumab + CHOP100.0
Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI) Secondary · From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)

SDI 120 is a shorter duration infusion of 120 minutes and SDI 90 is shorter duration infusion of 90 minutes. Grade 3 IRR AE: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae. Grade 4 IRR AE: Life-threatening consequences; urgent intervention indicated.

SDI 120 (n=5)
GroupValue95% CI
Obinutuzumab + CHOP0
SDI 90 (n=70)
GroupValue95% CI
Obinutuzumab + CHOP0
Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab Secondary · Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12

Blood was collected for PK Parameters. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in micrograms per milliliter (μg/mL).

Cycle 1
GroupValue95% CI
Obinutuzumab + CHOP297± 110
Cycle 8 (n = 85)
GroupValue95% CI
Obinutuzumab + CHOP574± 183
Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab Secondary · Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12

T1/2 is the time required for the concentration of the drug to reach half of its original value. Blood was collected for PK Parameters. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in days

Cycle 1 (n = 37)
GroupValue95% CI
Obinutuzumab + CHOP6.04± 1.54
Cycle 8 (n = 21)
GroupValue95% CI
Obinutuzumab + CHOP23± 15.9
Pharmacokinetics: Clearance (Cl) for Obinutuzumab Secondary · Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12

Cl is the volume of serum cleared of the drug per unit of time. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in milliliters/day (mL/day).

Cycle 1 (n = 54)
GroupValue95% CI
Obinutuzumab + CHOP456± 254
Cycle 8 (n = 37)
GroupValue95% CI
Obinutuzumab + CHOP143± 59.8
Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab Secondary · Cycle 1 Day 1 pre and post dose, Days 3,5, Day 8 pre and post-dose, Day 15 pre-dose. Cycle 8 Day 1 pre and post-dose, Days 5,8,12

V is the apparent volume in which a drug is distributed in the body. Serum samples were sent to a central lab and were analyzed for obinutuzumab using a validated enzyme-linked immunosorbent assay (ELISA) measured in milliliters (mL).

Cycle 1 (n = 54)
GroupValue95% CI
Obinutuzumab + CHOP4580± 2450
Cycle 8 (n = 37)
GroupValue95% CI
Obinutuzumab + CHOP9210± 17000

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of study treatment to clinical data cut-off: 23 December 2016 (up to 5 years, 4 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Obinutuzumab + CHOP
Serious: 38/100 (38%)
Deaths:

Serious adverse events (53 terms)

ReactionSystemObinutuzumab + CHOP
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
SepsisInfections and infestations
DiarrhoeaGastrointestinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
Mental status changesPsychiatric disorders
Catheter site cellulitisInfections and infestations
CellulitisInfections and infestations
Clostridium difficile infectionInfections and infestations
Pneumonia cytomegaloviralInfections and infestations
Device related infectionInfections and infestations
EncephalitisInfections and infestations
Enterococcal infectionInfections and infestations
Herpes zosterInfections and infestations
Herpes zoster disseminatedInfections and infestations
Colonic abscessInfections and infestations
Localised infectionInfections and infestations
Pneumonia legionellaInfections and infestations
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Other adverse events (60 terms — click to expand)

ReactionSystemObinutuzumab + CHOP
NauseaGastrointestinal disorders
Infusion related reactionInjury, poisoning and procedural complications
FatigueGeneral disorders
ChillsGeneral disorders
AlopeciaSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
Neuropathy peripheralNervous system disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
DizzinessNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
HypotensionVascular disorders
StomatitisGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Bone painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Abdominal painGastrointestinal disorders
Weight decreasedInvestigations
Mucosal inflammationGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HypokalaemiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
Oedema peripheralGeneral disorders
Dry mouthGastrointestinal disorders
Urinary tract infectionInfections and infestations
TachycardiaCardiac disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Chest painGeneral disorders
DysgeusiaNervous system disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Febrile neutropenia, Pneumonia, Sepsis, Diarrhoea, Hypoxia, Pulmonary embolism, Dehydration, Mental status changes.

Data from ClinicalTrials.gov NCT01414855 adverse events section.

Sponsor's own description

This open-label, multicenter study will evaluate the efficacy and safety of obinutuzumab \[RO5072759 (GA101)\] in combination with CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) chemotherapy in patients with advanced diffuse large B-cell lymphoma. Patients will receive 8 cycles of obinutuzumab (1000 mg intravenously on Day 1 of each 21-day cycle, during Cycle 1 obinutuzumab will also be infused on Days 8 and 15) in combination with CHOP chemotherapy on Day 1 of cycles 1 to 6. A substudy will investigate the drug-drug interaction of obinutuzumab with CHOP chemotherapy agents. For the substudy, an additional cohort of approximately 15 patients are planned to be enrolled at a subset of investigational sites.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A Review of Obinutuzumab (GA101), a Novel Type II Anti-CD20 Monoclonal Antibody, for the Treatment of Patients with B-Cell Malignancies.
    Tobinai K, Klein C, Oya N, Fingerle-Rowson G. · · 2017 · cited 128× · PMID 28004361 · DOI 10.1007/s12325-016-0451-1
  2. Obinutuzumab in the treatment of B-cell malignancies: a comprehensive review.
    Davies A, Kater AP, Sharman JP, Stilgenbauer S, et al · · 2022 · cited 23× · PMID 35856239 · DOI 10.2217/fon-2022-0112
  3. Obinutuzumab plus CHOP is effective and has a tolerable safety profile in previously untreated, advanced diffuse large B-cell lymphoma: the phase II GATHER study.
    Sharman JP, Forero-Torres A, Costa LJ, Flinn IW, et al · · 2019 · cited 14× · PMID 30277102 · DOI 10.1080/10428194.2018.1515940
  4. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study.
    Gibiansky E, Gibiansky L, Buchheit V, Frey N, et al · · 2019 · cited 9× · PMID 31050355 · DOI 10.1111/bcp.13974
  5. Pharmacokinetics of obinutuzumab in Chinese patients with B-cell lymphomas.
    Zhai J, Qin Y, Zhu J, Song Y, et al · · 2017 · cited 7× · PMID 28072473 · DOI 10.1111/bcp.13232
  6. Rituximab-Based Therapy in Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: Individualized Risk-Adapted Therapy Approach Using Molecular Subtypes.
    Fan L, Li L, Zhou Y, Li J. · · 2017 · cited 6× · PMID 32300390 · DOI 10.14740/jh320w

Verify or expand the search:

Other trials of obinutuzumab

Trials testing the same drug.

Other recruiting trials for Lymphoma, B-Cell

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Other Genentech, Inc. trials

Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01414855.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing