- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03817853
An Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion in Patients With Previously Untreated Advanced Follicular Lymphoma
A Multicentric, Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion (SDI) in Patients With Previously Untreated Advanced Follicular Lymphoma
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
CE
-
Fortaleza, CE, Brazil, 60115-281
- NOHC - Núcleo de Oncologia e Hematologia do Ceará
-
-
RS
-
Porto Alegre, RS, Brazil, 90035-903
- Hospital das Clinicas - UFRGS
-
-
SP
-
Jau, SP, Brazil, 17210-120
- Hospital Amaral Carvalho
-
-
-
-
-
Chemnitz, Germany, 09113
- Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Hämatologie und Onkologie
-
Dessau-Roßlau, Germany, 06847
- Städtisches Klinikum Dessau
-
Frankfurt, Germany, 60596
- Universitätsklinikum Frankfurt; Medizinische Klinik II; Onkologie
-
Hamburg, Germany, 22081
- OncoResearch Lerchenfeld GmbH
-
Köln, Germany, 50937
- Klinik der Uni zu Köln; I. Med. Klinik
-
Landshut, Germany, 84036
- MVZ Dr. Vehling-Kaiser GmbH; Onkologische Praxis
-
Lübeck, Germany, 23562
- Onkologische Schwerpunktpraxis Lübeck
-
-
-
-
-
Chiba, Japan, 260-8717
- Chiba Cancer Center
-
Hokkaido, Japan, 060-8648
- Hokkaido University Hospital
-
Hyogo, Japan, 650-0047
- Kobe City Medical Center General Hospital
-
Osaka, Japan, 589-8511
- Kindai University Hospital
-
Tokyo, Japan, 104-0045
- National Cancer Center Hospital
-
Tokyo, Japan, 135-8550
- The Cancer Institute Hospital of JFCR
-
-
-
-
-
Dordrecht, Netherlands, 3318 AT
- Albert Schweitzer Ziekenhuis - loc Dordrecht
-
Groningen, Netherlands, 9728 NT
- Martini Ziekenhuis
-
-
-
-
-
Barcelona, Spain, 08003
- Hospital del Mar; Servicio de Hematologia
-
Madrid, Spain, 28046
- Hospital Universitario la Paz; Servicio de Hematologia
-
Murcia, Spain, 30008
- Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
-
-
Alava
-
Vitoria, Alava, Spain, 01009
- Hospital De Txagorritxu; Servicio de Hematologia
-
-
Cadiz
-
Cádiz, Cadiz, Spain, 11009
- Hospital Universitario Puerta del Mar; Servicio de Hematologia
-
-
-
-
-
Cardiff, United Kingdom, CF14 4XW
- University Hospital of Wales
-
Portsmouth, United Kingdom, PO6 3LY
- Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
-
Truro, United Kingdom, TR1 3LQ
- Royal Cornwall Hospital
-
-
-
-
Colorado
-
Boulder, Colorado, United States, 80303
- Rocky Mountain Cancer Center; Medical Oncology
-
-
Maryland
-
Bethesda, Maryland, United States, 20817-1915
- American Oncology Partners of Maryland, PA
-
-
New Jersey
-
Florham Park, New Jersey, United States, 07932
- Summit Medical Center
-
-
New Mexico
-
Farmington, New Mexico, United States, 87401
- San Juan Oncology Associates
-
-
Oregon
-
Eugene, Oregon, United States, 97401-8122
- Willamette Valley Cancer Ctr - 520 Country Club
-
-
Texas
-
Austin, Texas, United States, 78731
- Texas Onc-Central Austin CA Ct
-
Austin, Texas, United States, 78731
- Texas Oncology Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Patients with previously untreated Stage III or IV FL or Stage II bulky disease scheduled to receive obinutuzumab plus chemotherapy due to at least one of the following criteria: a.) Bulky disease, defined as a nodal or extranodal (except spleen) mass
≥ 7 cm in the greatest diameter b.) Local symptoms or compromise of normal organ function due to progressive nodal disease or extranodal tumor mass c.) Presence of B symptoms (fever [> 38ºC], drenching night sweats, or unintentional weight loss of > 10% of normal body weight over a period of 6 months or less) d.) Presence of symptomatic extranodal disease (e.g., pleural effusions, peritoneal ascites) e.) Cytopenias due to underlying lymphoma (i.e., absolute neutrophil count < 1.0 × 109/L, hemoglobin < 10 g/dL, and/or platelet count < 100 × 109/L) f.) Involvement of ≥ 3 nodal sites, each with a diameter of ≥ 3 cm g.) Symptomatic splenic enlargement
- Histologically documented CD-20-positive FL, as determined by the local laboratory
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Adequate hematologic function (unless abnormalities are related to FL)
- Life expectancy of ≥ 12 months
- For women who are not postmenopausal (≥ 12 consecutive months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 18 months after the last dose of obinutuzumab, for at least 3 months after the last dose of bendamustine or according to institutional guidelines for CHOP or CVP chemotherapy, whichever is longer
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
Exclusion Criteria:
- Relapsed / refractory FL
- Prior treatment for FL with chemotherapy, radiotherapy, or immunotherapy
- Grade IIIb FL
- Histological evidence of transformation of FL into high-grade B-cell NHL
- Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone/prednisolone/methylprednisolone (at a dose equivalent to >30 mg/day prednisone), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1
- History of solid organ transplantation
- History of anti-CD20 antibody therapy
- History of severe allergic or anaphylactic reaction to humanized, chimeric, or murine monoclonal antibodies
- Known sensitivity or allergy to murine products
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any of the study drugs
- Active bacterial, viral, fungal, or other infection or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1
- Positive test results for chronic HBV infection (defined as positive HBsAg serology)
- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
- Known history of HIV positive status
- History of progressive multifocal leukoencephalopathy (PML)
- Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1 or anticipation that such a live, attenuated vaccine will be required during the study
- History of prior other malignancy with the exception of: a. Curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal- or squamous-cell skin cancer, Stage I melanoma, or low-grade, early-stage localized prostate cancer b. Any previously treated malignancy that has been in remission without treatment for ≥ 2 years prior to enrollment
- Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
- Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1, Day 1, or anticipation of a major surgical procedure during the course of the study
Any of the following abnormal laboratory values:
- Creatinine > 1.5 × the upper limit of normal (ULN) (unless creatinine clearance normal) or creatinine clearance < 40 mL/min
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN
- Total bilirubin ≥ 1.5 × the ULN: Patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN.
- International normalized ratio (INR) > 1.5 in the absence of therapeutic anticoagulation
- Partial thromboplastin time or activated partial thromboplastin time > 1.5 × ULN in the absence of a lupus anticoagulant
- For patients who will be receiving CHOP: left ventricular ejection fraction (LVEF) < 50% by multigated acquisition (MUGA) scan or echocardiogram
- Pregnant or lactating, or intending to become pregnant during the study
- Any investigational therapy within 28 days prior to the start of Cycle 1
- Positive test results for human T-lymphotropic virus 1 (HTLV-1)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Obinutuzumab+Chemotherapy
Participants received 6-8 cycles of obinutuzumab, combined with 6 or 8 cycles of standard chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone/methylprednisolone [CHOP - 21-day cycle) or bendamustine (28-day cycle), or cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone [CVP - 21-day cycle]).
Participants received an additional two doses of obinutuzumab on Days 8 and 15 of Cycle 1.
The investigator is free to choose the chemotherapy for each patient.
Obinutuzumab and chemotherapy is administered during induction phase and obinutuzumab monotherapy is administered during maintenance phase.
|
Obinutuzumab 1000 mg IV infusion, administered on Day 1, 8 and 15 during Cycle 1, and on Day 1 of subsequent cycles, for 6-8 cycles.
Each cycle is 21 or 28 days long depending on the chemotherapy regimen allocated.
Maintenance obinutuzumab monotherapy in patients who achieve at least a partial response, after induction therapy will be administered a dose of 1000 mg once every 8 weeks for 2 years or until disease progression (whichever occurs first).
Other Names:
Bendamustine will be administered on Days 1 and 2 for Cycles 1-6 at a dose of 90 mg/m2/day, for six 28-day cycles.
Cyclophosphamide 750 milligrams per square metre (mg/m^2), administered intravenously (IV) on Day 1 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.
Doxorubicin 50 mg/m^2 IV, administered on Day 1 of each 21-day cycle, for six cycles.
Prednisone 100 mg (or equivalent prednisolone or methylprednisolone), administered orally on Days 1-5 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.
Vincristine 1.4 mg/m^2 (maximum 2 mg) IV, administered on Day 1 of each 21-day cycle, for six cycles for CHOP treatment or eight cycles for CVP treatment.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Grade >=3 Infusion-Related Reactions (IRRs) During Cycle 2 in Patients Who Had Previously Received Obinutuzumab at the Standard Infusion Rate During Cycle 1 Without Experiencing a Grade 3 or 4 IRR
Time Frame: Within 24 hours from the end of study treatment infusion of Day 1 in Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
|
IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.
|
Within 24 hours from the end of study treatment infusion of Day 1 in Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of IRRs Regardless of Grade by Cycle
Time Frame: Within 24 hours from the end of study treatment infusion in all cycles, including maintenance ((1 cycle: 21 or 28 days depending on the chemotherapy selected); up to approximately 2.5 years)
|
IRRs were defined as all adverse events (AEs) that occurred during or within 24 hours from the end of study treatment infusion and were judged as related to infusion of study treatment components by the investigator.
|
Within 24 hours from the end of study treatment infusion in all cycles, including maintenance ((1 cycle: 21 or 28 days depending on the chemotherapy selected); up to approximately 2.5 years)
|
Time to IRR From Infusion to Onset of the IRR During Cycle 2
Time Frame: From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
|
Time to IRR (of any grade) in Cycle 2 was defined as the time from the start of infusion (i.e., start date/time of infusion of the first component of study treatment) in Cycle 2 to the onset of the IRR (of any grade) during Cycle 2.
|
From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)
|
Duration (In Minutes) of Obinutuzumab Administration by Cycle
Time Frame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
|
The duration of obinutuzumab administration (in minutes) by cycle was defined as the difference between the end time and the start time of obinutuzumab administration.
|
All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
|
Type of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
Time Frame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
|
All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
|
|
Duration of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
Time Frame: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
|
The duration, in minutes, of IRRs during all cycles, where obinutuzumab was administered as an SDI.
|
All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)
|
Objective Response Rate (ORR) at the End of Induction (EOI) Therapy
Time Frame: Baseline up to end of induction therapy (up to approximately 6 months)
|
ORR at EOI therapy was defined as the percentage of particpants with either a CR, CR unconfirmed or PR at the EOI visit, as determined by the investigator and according to the guidelines used at the site.
|
Baseline up to end of induction therapy (up to approximately 6 months)
|
Progression-Free Survival (PFS) Rate at the End of the Study
Time Frame: Baseline up to end of study (up to approximately 4 years)
|
PFS was defined as the time from start of treatment to the first occurrence of disease progression as assessed by the investigator according to the guidelines used at the site or death from any cause.
|
Baseline up to end of study (up to approximately 4 years)
|
Overall Survival (OS) at the End of the Study
Time Frame: Baseline up to end of study (up to approximately 4 years)
|
OS was defined as the time from start of treatment (date of first intake of any study treatment component) to death from any cause.
|
Baseline up to end of study (up to approximately 4 years)
|
Complete Response (CR) Rate at 30 Months (CR30), as Assessed by the Investigator and According to the Guidelines Used at the Site
Time Frame: Baseline up to 30 months
|
The CR30 rate was defined as the percentage of participants with a CR at 30 months from study treatment initiation (date of first intake of any study treatment component), as determined by the investigator according to the guidelines used at the site.
|
Baseline up to 30 months
|
Percentage of Participants With Adverse Events (AEs)
Time Frame: Baseline up to end of study (approximately 4 years)
|
An AE was defined as any untoward medical occurrence in a clinical investigation participant who was administered a pharmaceutical product, regardless of causal attribution.
An AE was therefore any unfavourable 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.
Pre-existing conditions which worsened during the study, recurrence of an intermittent medical condition, deterioration in a laboratory value or other clinical test or were related to a protocol-mandated intervention were also considered AEs.
Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
|
Baseline up to end of study (approximately 4 years)
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Follicular
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Antibiotics, Antineoplastic
- Prednisolone
- Methylprednisolone
- Cyclophosphamide
- Bendamustine Hydrochloride
- Prednisone
- Doxorubicin
- Vincristine
- Obinutuzumab
Other Study ID Numbers
- MO40597
- 2018-003255-38 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Follicular Lymphoma
-
Joseph TuscanoNational Cancer Institute (NCI); Genentech, Inc.; Pharmacyclics LLC.RecruitingAnn Arbor Stage II Follicular Lymphoma | Ann Arbor Stage III Follicular Lymphoma | Ann Arbor Stage IV Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
-
Epizyme, Inc.CompletedB-cell Lymphomas (Phase 1) | Advanced Solid Tumors (Phase 1) | Diffuse Large B-cell Lymphoma (Phase 2) | Follicular Lymphoma (Phase 2) | Transformed Follicular Lymphoma | Primary Mediastinal Large B-Cell LymphomaAustralia, Canada, France, Germany, Italy, Poland, Taiwan, Ukraine, United Kingdom, United States
-
National Cancer Institute (NCI)TerminatedStage III Grade 1 Follicular Lymphoma | Stage III Grade 2 Follicular Lymphoma | Stage III Grade 3 Follicular Lymphoma | Stage IV Grade 1 Follicular Lymphoma | Stage IV Grade 2 Follicular Lymphoma | Stage IV Grade 3 Follicular LymphomaUnited States
-
National Cancer Institute (NCI)RecruitingRecurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
-
Memorial Sloan Kettering Cancer CenterFox Chase Cancer Center; Pharmacyclics LLC.TerminatedFollicular Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma, Grade 2 | Follicular Lymphoma Grade IIIaUnited States
-
Olivia Newton-John Cancer Research InstituteBristol-Myers Squibb; Barwon Health; Austin Health; Eastern Health; Fiona Stanley... and other collaboratorsRecruitingFollicular Lymphoma Stage II | Follicular Lymphoma Stage III | Follicular Lymphoma Stage IVAustralia
-
Robert LowskyNational Cancer Institute (NCI); Janssen, LP; The Leukemia and Lymphoma Society; Rising Tide FoundationCompletedMantle Cell Lymphoma | Marginal Zone Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
-
Massachusetts General HospitalTG TherapeuticsActive, not recruitingLymphoma | Follicular Lymphoma | Marginal Zone Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma Grade IIIa | Marginal Zone B Cell Lymphoma | Follicular Lymphoma Grade 2United States
-
Fondazione Italiana Linfomi ONLUSCompletedFollicular Lymphoma, Grade 1 | Follicular Lymphoma, Grade 2 | Follicular Lymphoma Grade 3AItaly
-
National Cancer Institute (NCI)Celgene CorporationActive, not recruitingAnn Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma | Ann Arbor Stage II Grade 3 Non-Contiguous... and other conditionsUnited States
Clinical Trials on Obinutuzumab
-
Institute of Hematology & Blood Diseases Hospital...RecruitingImmune Thrombocytopenia | TreatmentChina
-
Qianfoshan HospitalNot yet recruitingIdiopathic Membranous Nephropathy
-
Michael ChoiPharmacyclics LLC.Withdrawn
-
Institute of Hematology & Blood Diseases HospitalRecruitingImmune Thrombocytopenia | TreatmentChina
-
Hoffmann-La RocheCompletedFollicular Lymphoma | Chronic Lymphocytic LeukemiaKorea, Republic of
-
French Innovative Leukemia OrganisationHoffmann-La RocheRecruiting
-
The First Affiliated Hospital with Nanjing Medical...RecruitingObinutuzumab | Rapid Infusion | Intravenous Infusion ReactionChina
-
Fondazione Italiana Linfomi - ETSRoche Pharma AGRecruiting
-
TG Therapeutics, Inc.CompletedChronic Lymphocytic LeukemiaUnited States
-
Paolo GhiaRecruitingChronic Lymphocytic LeukemiaItaly