An Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion in Patients With Previously Untreated Advanced Follicular Lymphoma

NCT03817853 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: MO405972018-003255-38
• Study Type: interventional
• Target: 114
• Locations: 7 countries
• Sites: 33

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.

Conditions

Advanced Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (10)

• Percentage of Participants With Adverse Events (AEs)

  Baseline up to end of study (approximately 4 years)

• 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)

• 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)

• 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)

Study Arms (1)

Obinutuzumab+Chemotherapy

EXPERIMENTAL

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.

Drug: Obinutuzumab; Drug: Bendamustine; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone/Prednisolone/Methylprednisolone; Drug: Vincristine

Interventions

Obinutuzumab DRUG

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).

Also known as: GA101, RO5072759

Obinutuzumab+Chemotherapy

Bendamustine DRUG

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.

Obinutuzumab+Chemotherapy

Cyclophosphamide DRUG

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.

Obinutuzumab+Chemotherapy

Doxorubicin DRUG

Doxorubicin 50 mg/m\^2 IV, administered on Day 1 of each 21-day cycle, for six cycles.

Obinutuzumab+Chemotherapy

Prednisone/Prednisolone/Methylprednisolone DRUG

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.

Obinutuzumab+Chemotherapy

Vincristine DRUG

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.

Obinutuzumab+Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (33)

Rocky Mountain Cancer Center; Medical Oncology

Boulder, Colorado, 80303, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817-1915, United States

Location

Summit Medical Center

Florham Park, New Jersey, 07932, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Willamette Valley Cancer Ctr - 520 Country Club

Eugene, Oregon, 97401-8122, United States

Location

Texas Onc-Central Austin CA Ct

Austin, Texas, 78731, United States

Location

Texas Oncology Cancer Center

Austin, Texas, 78731, United States

Location

NOHC - Núcleo de Oncologia e Hematologia do Ceará

Fortaleza, Ceará, 60115-281, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Hämatologie und Onkologie

Chemnitz, 09113, Germany

Location

Klinik der Uni zu Köln; I. Med. Klinik

Cologne, 50937, Germany

Location

Städtisches Klinikum Dessau

Dessau, 06847, Germany

Location

Universitätsklinikum Frankfurt; Medizinische Klinik II; Onkologie

Frankfurt, 60596, Germany

Location

OncoResearch Lerchenfeld GmbH

Hamburg, 22081, Germany

Location

MVZ Dr. Vehling-Kaiser GmbH; Onkologische Praxis

Landshut, 84036, Germany

Location

Onkologische Schwerpunktpraxis Lübeck

Lübeck, 23562, Germany

Location

Chiba Cancer Center

Chiba, 260-8717, Japan

Location

Hokkaido University Hospital

Hokkaido, 060-8648, Japan

Location

Kobe City Medical Center General Hospital

Hyōgo, 650-0047, Japan

Location

Kindai University Hospital

Osaka, 589-8511, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Albert Schweitzer Ziekenhuis - loc Dordrecht

Dordrecht, 3318 AT, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Hospital De Txagorritxu; Servicio de Hematologia

Vitoria-Gasteiz, Alava, 01009, Spain

Location

Hospital Universitario Puerta del Mar; Servicio de Hematologia

Cadiz, Cadiz, 11009, Spain

Location

Hospital del Mar; Servicio de Hematologia

Barcelona, 08003, Spain

Location

Hospital Universitario la Paz; Servicio de Hematologia

Madrid, 28046, Spain

Location

Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología

Murcia, 30008, Spain

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital

Portsmouth, PO6 3LY, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LQ, United Kingdom

Location

MeSH Terms

Interventions

obinutuzumab; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 28, 2019
• Study Start: February 26, 2019
• Primary Completion: August 4, 2020
• Study Completion: January 25, 2023
• Last Updated: April 4, 2024
• Results First Posted: August 24, 2021

Record last verified: 2024-03

Locations

NL (2); GB (3); BR (3); ES (5); DE (7); US (7); JP (6)