Studie obinutuzumabu [RO5072759 (GA101)] v kombinaci s chemoterapií CHOP u pacientů s dříve neléčeným pokročilým difuzním velkým B-buněčným lymfomem (GATHER)
Fáze II, otevřená, multicentrická studie účinnosti, bezpečnosti a biomarkerů u pacientů s dříve neléčeným pokročilým difuzním velkým B-lymfomem z B-buněk léčených GA101 (RO5072759) v kombinaci s CHOP chemoterapií
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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
-
-
Alabama
-
Birmingham, Alabama, Spojené státy, 35294-3300
- University of Alabama at Birmingham
-
-
California
-
Encinitas, California, Spojené státy, 92024
- cCare
-
-
Colorado
-
Aurora, Colorado, Spojené státy, 80045
- University of Colorado Cancer Center Department of Hematology
-
Denver, Colorado, Spojené státy, 80218
- Rocky Mountain Cancer Ctr - Denver (Williams)
-
-
Connecticut
-
Norwalk, Connecticut, Spojené státy, 06856
- Norwalk Hospital
-
-
Florida
-
Fort Myers, Florida, Spojené státy, 33901-8101
- Florida Cancer Specialists; Department of Oncology
-
St. Petersburg, Florida, Spojené státy, 33719
- Florida Cancer Specialists; Saint Petersburg
-
-
Georgia
-
Marietta, Georgia, Spojené státy, 30060
- Northwest Georgia Oncology Centers PC - Marietta
-
-
Idaho
-
Coeur d'Alene, Idaho, Spojené státy, 83814
- Kootenai Medical Center
-
-
Illinois
-
Chicago, Illinois, Spojené státy, 60611
- Northwestern University; Robert H. Lurie Comp Can Ctr
-
Peoria, Illinois, Spojené státy, 61615-7828
- Onc Hem Assoc of Central IL
-
-
Iowa
-
Ames, Iowa, Spojené státy, 50010
- McFarland Clinic
-
-
Kentucky
-
Louisville, Kentucky, Spojené státy, 40245
- Jewish Cancer Care
-
-
Massachusetts
-
Worcester, Massachusetts, Spojené státy, 01655
- University of Massachusetts Medical School
-
-
Michigan
-
Ann Arbor, Michigan, Spojené státy, 48109-0934
- University of Michigan
-
-
Montana
-
Missoula, Montana, Spojené státy, 59802
- MT Cancer Inst Fndtn; MT Can Spec
-
-
Nevada
-
Las Vegas, Nevada, Spojené státy, 89128
- Comprehensive Cancer Centers of Nevada
-
-
New Jersey
-
Basking Ridge, New Jersey, Spojené státy, 07920
- MSKCC at Basking Ridge
-
Hackensack, New Jersey, Spojené státy, 07601
- Hackensack University Medical Center
-
-
New Mexico
-
Farmington, New Mexico, Spojené státy, 87401
- San Juan Oncology Associates
-
-
New York
-
Commack, New York, Spojené státy, 11725
- Memorial Sloan-Kettering; Cancer Center
-
New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering Cancer Center
-
Rockville Centre, New York, Spojené státy, 11570
- MSKCC at Mercy Med Ctr
-
Sleepy Hollow, New York, Spojené státy, 10591
- MSKCC at Sleepy Hollow
-
-
North Carolina
-
High Point, North Carolina, Spojené státy, 27262
- Emerywood Hematology and Onc
-
-
Oregon
-
Springfield, Oregon, Spojené státy, 97477
- Willamette Valley Cancer Insitute and Research Center
-
-
South Carolina
-
Charleston, South Carolina, Spojené státy, 29425
- Medical University of SC (MUSC)
-
-
Tennessee
-
Nashville, Tennessee, Spojené státy, 37203
- SCRI-Tennessee Oncology
-
-
Texas
-
Fort Worth, Texas, Spojené státy, 76177
- Onc & Hem Assoc; USO Cent Pharm
-
Houston, Texas, Spojené státy, 77030
- Methodist Hospital Research Institute
-
Houston, Texas, Spojené státy, 77030
- MD Anderson Cancer Center Department of Lymphoma & Myeloma
-
San Antonio, Texas, Spojené státy, 78229
- Cancer Therapy & Research Center
-
Tyler, Texas, Spojené státy, 75702
- USO - Tyler Cancer Ctr
-
-
Virginia
-
Roanoke, Virginia, Spojené státy, 24014
- Blue Ridge Cancer Care - Roanoke
-
-
Washington
-
Spokane, Washington, Spojené státy, 99208
- Medical Oncology Associates
-
Vancouver, Washington, Spojené státy, 98684
- Northwest Cancer Specialists - Vancouver
-
Yakima, Washington, Spojené státy, 98902
- Yakima Valley Memorial Hospital/North Star Lodge
-
-
Wisconsin
-
Green Bay, Wisconsin, Spojené státy, 54311
- Aurora Bay Care Medical Center
-
-
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Adult patients, ≥18 years of age
- Previously untreated cluster of differentiation antigen 20 (CD20)-positive diffuse large B-cell lymphoma
- Ann Arbour Stage III/IV and bulky II (mass >10 cm)
- At least one bi-dimensionally measurable lesion defined as >1.5 cm in its largest dimension by CT scan
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Left ventricular ejection fraction ≥50%
- Adequate hematologic function
Exclusion Criteria:
- Transformed lymphoma (follicular IIIB) if previously treated with chemotherapy or immunotherapy
- Prior therapy for diffuse large B-cell lymphoma except for nodal biopsy or local irradiation
- Central nervous system (CNS) lymphoma, primary mediastinal large cell lymphoma, primary cutaneous lymphoma, primary effusion lymphoma
- Patients who received cytotoxic drugs or rituximab as part of their treatment for another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody
- Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
- Contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- History of other malignancy, except for curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix, or malignancy treated with or without curative intent and in remission without treatment for ≥2 years prior to enrolment
- Positive for hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV-1) infection
- Pregnant or lactating women
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Experimentální: obinutuzumab + CHOP
Participants received 1000 mg obinutuzumab intravenously on Day 1 of each 21-day cycle for 8 cycles; during Cycle 1 administration also on Days 8 and 15. Participants also received standard CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisone) for 6 cycles. |
1000 mg intravenously on Day 1 of each 21-day cycle, 8 cycles; during Cycle 1 administration also on Days 8 and 15. 750 mg/m^2 intravenous (IV), Day 1 of each 21-day cycle, 6 cycles. 50 mg/m^2 IV, Day 1 of each 21-cycle, 6 cycles. 100 mg/day, Days 1 through 5 of each 21-day cycle, 6 cycles. 1.4 mg/m^2 IV, Day 1 of each 21-day cycle, 6 cycles. |
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Complete Response (CR) Rate as Assessed by the Investigator at the End of Treatment
Časové okno: 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. |
From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
|
|
Overall Response Rate (ORR) as Assessed by the Investigator at the End of Treatment
Časové okno: 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. |
From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Complete Response (CR) Rate as Assessed by the Independent Review Facility (IRF) at the End of Treatment
Časové okno: 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. |
From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
|
|
Overall Response Rate (ORR) as Assessed by the IRF at the End of Treatment
Časové okno: 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. |
From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
|
|
Progression-Free Survival (PFS) as Assessed by the Investigator
Časové okno: 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. |
From the first dose of study treatment to PFS assessment (up to 64 months)
|
|
Duration of Response (DOR)
Časové okno: 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. |
From the response assessment to relapse, progression, or death (up to 64 months)
|
|
Percentage of Participants With Adverse Events as a Measure of Safety
Časové okno: 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. |
From the first dose of study treatment to end of study (up to 5 years 4 months)
|
|
Number of Participants With Grade 3 to 4 Infusion-Related (IRR) Adverse Events (AE) in Participants Receiving Shorter Duration Infusion (SDI)
Časové okno: 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. |
From the first dose of study treatment to end of treatment response assessment (approximately 228 to 258 days)
|
|
Pharmacokinetics (PK): Maximum Concentration Observed (Cmax) for Obinutuzumab
Časové okno: 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 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
|
|
Pharmacokinetics: Terminal Half-Life (t1/2) for Obinutuzumab
Časové okno: 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 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
|
|
Pharmacokinetics: Clearance (Cl) for Obinutuzumab
Časové okno: 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 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
|
|
Pharmacokinetics: Volume of Distribution (V) for Obinutuzumab
Časové okno: 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 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
|
|
Pharmacokinetics: Area Under the Concentration-Time Curve 7 Day (AUC7day)
Časové okno: 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 in day times micrograms per milliliter (day*μg/mL). |
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
|
|
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Depletion
Časové okno: From end of study treatment up to approximately 30 months
|
B-cell depletion was defined as a CD19 result < 0.07 × 10^9/L after at least one dose of study drug had been administered. Participants were evaluated during a 30-month post-treatment follow-up period following the completion of active study treatment (Cycle 8 [each cycle = 21 days]). Total study duration across active treatment and follow-up was up to approximately 5 years. |
From end of study treatment up to approximately 30 months
|
|
Pharmacodynamics: Number of Participants With Peripheral Blood B-cell Recovery
Časové okno: Up to approximately 30 months
|
B-cell recovery was defined as a CD19 result >= 0.07 × 10^9/L, where CD19 was previously depleted. B-cell recovery was only considered possible following the last dose of study treatment. The number of participants with B-cell recovery from End of Treatment to 6 months of Follow-up is reported in two categories: Recovery with Progressive Disease (PD) [PD before B-cell recovery or PD within 45 days after recovery] or Recovery without PD. PD required one of the following: 50% increase in the absolute number of circulating lymphocytes, Appearance of new palpable lymph nodes, 50% increase in the longest diameter of any previous site of lymphadenopathy, 50% increase in the enlargement of the liver and/or spleen or Transformation to a more aggressive histology. |
Up to approximately 30 months
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Ředitel studie: Clinical Trials, Genentech, Inc.
Publikace a užitečné odkazy
Obecné publikace
- Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
- Sharman JP, Forero-Torres A, Costa LJ, Flinn IW, Inhorn L, Kelly K, Bessudo A, Fayad LE, Kaminski MS, Evens AM, Flowers CR, Sahin D, Mundt KE, Sandmann T, Fingerle-Rowson G, Vignal C, Mobasher M, Zelenetz AD. 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. Leuk Lymphoma. 2019 Apr;60(4):894-903. doi: 10.1080/10428194.2018.1515940. Epub 2018 Oct 2.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhadovaný)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Novotvary
- Onemocnění imunitního systému
- Novotvary podle histologického typu
- Lymfatická onemocnění
- Lymfoproliferativní poruchy
- Imunoproliferativní poruchy
- Lymfom, Non-Hodgkin
- Lymfom
- Hemická a lymfatická onemocnění
- Lymfom, B-buňka
- Organické chemikálie
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Uhlovodíky
- Uhlovodíky, cyklické
- Uhlohydráty
- Alkaloidy
- Polycyklické aromatické uhlovodíky
- Uhlovodíky, aromatické
- Polycyklické sloučeniny
- Glykosidy
- Indoly
- Těhotenství
- Těhotenství
- Steroidy
- Sloučeniny roztaveného kruhu
- Fosforamidové hořčice
- Sloučeniny hořčice dusíku
- Hořčičné sloučeniny
- Uhlovodíky, halogenované
- Fosforamidy
- Organofosforové sloučeniny
- Těhotenství
- Vinca alkaloidy
- Alkaloidy tryptaminu sezologaninu
- Indolské alkaloidy
- Indolizidiny
- Indoliziny
- Antracykliny
- Nafthacenes
- Aminoglykosidy
- Daunorubicin
- Prednison
- Cyklofosfamid
- Doxorubicin
- Vinkristine
- Obinutuzumab
Další identifikační čísla studie
Další identifikační čísla studie
- GAO4915g
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .