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

NCT ID: NCT03817853

Last Updated: 2024-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-26
• Study Completion Date: 2023-01-25

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Obinutuzumab

Intervention Type: 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).

Bendamustine

Intervention Type: 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.

Cyclophosphamide

Intervention Type: 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.

Doxorubicin

Intervention Type: DRUG

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

Prednisone/Prednisolone/Methylprednisolone

Intervention Type: 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.

Vincristine

Intervention Type: 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.

Interventions

Obinutuzumab

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).

Intervention Type: DRUG

Bendamustine

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.

Intervention Type: DRUG

Cyclophosphamide

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.

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Prednisone/Prednisolone/Methylprednisolone

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.

Intervention Type: DRUG

Vincristine

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.

Intervention Type: DRUG

Other Intervention Names

GA101, RO5072759

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
• 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:

1. Creatinine > 1.5 × the upper limit of normal (ULN) (unless creatinine clearance normal) or creatinine clearance < 40 mL/min

2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN

3. Total bilirubin ≥ 1.5 × the ULN: Patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN.

4. International normalized ratio (INR) > 1.5 in the absence of therapeutic anticoagulation

5. 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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

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

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

Chemnitz, , Germany

Klinik der Uni zu Köln; I. Med. Klinik

Cologne, , Germany

Städtisches Klinikum Dessau

Dessau, , Germany

Universitätsklinikum Frankfurt; Medizinische Klinik II; Onkologie

Frankfurt, , Germany

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

MVZ Dr. Vehling-Kaiser GmbH; Onkologische Praxis

Landshut, , Germany

Onkologische Schwerpunktpraxis Lübeck

Lübeck, , Germany

Chiba Cancer Center

Chiba, , Japan

Hokkaido University Hospital

Hokkaido, , Japan

Kobe City Medical Center General Hospital

Hyōgo, , Japan

Kindai University Hospital

Osaka, , Japan

National Cancer Center Hospital

Tokyo, , Japan

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Albert Schweitzer Ziekenhuis - loc Dordrecht

Dordrecht, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Hospital De Txagorritxu; Servicio de Hematologia

Vitoria-Gasteiz, Alava, Spain

Hospital Universitario Puerta del Mar; Servicio de Hematologia

Cadiz, Cadiz, Spain

Hospital del Mar; Servicio de Hematologia

Barcelona, , Spain

Hospital Universitario la Paz; Servicio de Hematologia

Madrid, , Spain

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

Murcia, , Spain

University Hospital of Wales

Cardiff, , United Kingdom

Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital

Portsmouth, , United Kingdom

Royal Cornwall Hospital

Truro, , United Kingdom

Countries

United States; Brazil; Germany; Japan; Netherlands; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-003255-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO40597

Identifier Type: -

Identifier Source: org_study_id