This open-label, single arm study will evaluate the safety of obinutuzumab administered as a short duration infusion (SDI; target 90-minute infusion) during cycle 2 and from cycle 2 onwards in combination with chemotherapy in participants with previously untreated advanced follicular lymphoma (FL). The study has two phases: in the first phase, participants will receive the first cycle of obinutuzumab-based chemotherapy (G-chemo) induction therapy as usual with the first three infusions of obinutuzumab (1000 mg) administered at the regular infusion rate on Day 1, 8, and 15 of cycle 1. Phase 2 starts when participants who do not experience any Grade ≥ 3 infusion related reactions during the first cycle receive their first obintuzumab infusion given at the faster infusion rate in Cycle 2. For Cycle 2, Day 1 and all other following infusions (including maintenance), obinutuzumab will be administered at a faster infusion of 90-minute SDI, as long as the participant does not experience any Grade ≥ 3 infusion related reactions. The investigator is free to choose the chemotherapy for each participant (bendamustine, CHOP \[cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone/methylprednisolone\], or CVP \[cyclophosphamide, vincristine, and prednisone/prednisolone/methylprednisolone\]). The total number of cycles of G-chemo induction therapy and the cycles length depends on the chemotherapy chosen for each participant.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
114
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).
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.
Rocky Mountain Cancer Center; Medical Oncology
Boulder, Colorado, United States
American Oncology Partners of Maryland, PA
Bethesda, Maryland, United States
Summit Medical Center
Florham Park, New Jersey, United States
San Juan Oncology Associates
Farmington, New Mexico, United States
Willamette Valley Cancer Ctr - 520 Country Club
Eugene, Oregon, United States
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
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.
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)
Percentage of Participants With Adverse Events (AEs)
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.
Time frame: Baseline up to end of study (approximately 4 years)
Percentage of IRRs Regardless of Grade by Cycle
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.
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)
Time to IRR From Infusion to Onset of the IRR During Cycle 2
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.
Time frame: 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
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.
Time frame: 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)
Duration of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle
The duration, in minutes, of IRRs during all cycles, where obinutuzumab was administered as an SDI.
Time frame: 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
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.
Time frame: Baseline up to end of induction therapy (up to approximately 6 months)
Progression-Free Survival (PFS) Rate at the End of the Study
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.
Time frame: Baseline up to end of study (up to approximately 4 years)
Overall Survival (OS) at the End of the Study
OS was defined as the time from start of treatment (date of first intake of any study treatment component) to death from any cause.
Time frame: 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
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.
Time frame: Baseline up to 30 months
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Texas Onc-Central Austin CA Ct
Austin, Texas, United States
Texas Oncology Cancer Center
Austin, Texas, United States
NOHC - Núcleo de Oncologia e Hematologia do Ceará
Fortaleza, Ceará, Brazil
Hospital das Clinicas - UFRGS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Amaral Carvalho
Jaú, São Paulo, Brazil
...and 23 more locations