A Multicentric, Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion (SDI) in Patients With Previously Untreated Advanced Follicular Lymphoma
Overview
- Phase
- Phase 4
- Intervention
- Obinutuzumab
- Conditions
- Advanced Follicular Lymphoma
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 114
- Locations
- 33
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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.
Intervention: Obinutuzumab
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.
Intervention: Doxorubicin
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.
Intervention: Bendamustine
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.
Intervention: Cyclophosphamide
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.
Intervention: Prednisone/Prednisolone/Methylprednisolone
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.
Intervention: Vincristine
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Percentage of IRRs Regardless of Grade by Cycle(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(From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected))
- Type of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle(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(Baseline up to end of induction therapy (up to approximately 6 months))
- Duration (In Minutes) of Obinutuzumab Administration by Cycle(All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years))
- Progression-Free Survival (PFS) Rate at the End of the Study(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(Baseline up to 30 months)
- Percentage of Participants With Adverse Events (AEs)(Baseline up to end of study (approximately 4 years))
- Duration of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle(All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years))
- Overall Survival (OS) at the End of the Study(Baseline up to end of study (up to approximately 4 years))