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Advanced Follicular LymphomaPhase 4NCT03817853

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

A Phase 4 study testing Obinutuzumab, Bendamustine and Cyclophosphamide in people with Advanced Follicular Lymphoma, run by Hoffmann-La Roche at 33 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Follicular Lymphoma
What is being tested?
Obinutuzumab, Bendamustine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
114 participants
Where
33 sitesin 7 countries
Study dates
26 Feb 2019to 25 Jan 2023
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 29Show fewer
  • 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)

Trial locations and contacts

33 sites in 7 countries.

33 sites in 7 countries

United States7 sites

  • Texas Onc-Central Austin CA Ct

    Austin, Texas, 78731

  • Texas Oncology Cancer Center

    Austin, Texas, 78731

  • American Oncology Partners of Maryland, PA

    Bethesda, Maryland, 20817-1915

  • Rocky Mountain Cancer Center; Medical Oncology

    Boulder, Colorado, 80303

  • Willamette Valley Cancer Ctr - 520 Country Club

    Eugene, Oregon, 97401-8122

  • San Juan Oncology Associates

    Farmington, New Mexico, 87401

  • Summit Medical Center

    Florham Park, New Jersey, 07932

Other trials in United States

Germany7 sites

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

    Chemnitz, 09113

  • Klinik der Uni zu Köln; I. Med. Klinik

    Cologne, 50937

  • Städtisches Klinikum Dessau

    Dessau, 06847

  • Universitätsklinikum Frankfurt; Medizinische Klinik II; Onkologie

    Frankfurt, 60596

  • OncoResearch Lerchenfeld GmbH

    Hamburg, 22081

  • MVZ Dr. Vehling-Kaiser GmbH; Onkologische Praxis

    Landshut, 84036

  • Onkologische Schwerpunktpraxis Lübeck

    Lübeck, 23562

Other trials in Germany

Japan6 sites

  • Chiba Cancer Center

    Chiba, 260-8717

  • Hokkaido University Hospital

    Hokkaido, 060-8648

  • Kobe City Medical Center General Hospital

    Hyōgo, 650-0047

  • Kindai University Hospital

    Osaka, 589-8511

  • National Cancer Center Hospital

    Tokyo, 104-0045

  • The Cancer Institute Hospital of JFCR

    Tokyo, 135-8550

Other trials in Japan

Spain5 sites

  • Hospital del Mar; Servicio de Hematologia

    Barcelona, 08003

  • Hospital Universitario Puerta del Mar; Servicio de Hematologia

    Cadiz, Cadiz, 11009

  • Hospital Universitario la Paz; Servicio de Hematologia

    Madrid, 28046

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

    Murcia, 30008

  • Hospital De Txagorritxu; Servicio de Hematologia

    Vitoria-Gasteiz, Alava, 01009

Other trials in Spain

Brazil3 sites

  • NOHC - Núcleo de Oncologia e Hematologia do Ceará

    Fortaleza, Ceará, 60115-281

  • Hospital Amaral Carvalho

    Jaú, São Paulo, 17210-120

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-903

Other trials in Brazil

United Kingdom3 sites

  • University Hospital of Wales

    Cardiff, CF14 4XW

  • Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital

    Portsmouth, PO6 3LY

  • Royal Cornwall Hospital

    Truro, TR1 3LQ

Other trials in United Kingdom

Netherlands2 sites

  • Albert Schweitzer Ziekenhuis - loc Dordrecht

    Dordrecht, 3318 AT

  • Martini Ziekenhuis

    Groningen, 9728 NT

Other trials in Netherlands

About this study

Official title: A Multicentric, Open-Label, Single Arm Study of Obinutuzumab Short Duration Infusion (SDI) in Patients With Previously Untreated Advanced Follicular Lymphoma

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.

Being tested
Obinutuzumab, Bendamustine, Cyclophosphamide, Doxorubicin, Prednisone/Prednisolone/Methylprednisolone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ObinutuzumabDrug

    Also called GA101, RO5072759

    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).

  • BendamustineDrug

    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.

  • CyclophosphamideDrug

    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.

  • DoxorubicinDrug

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

  • Prednisone/Prednisolone/MethylprednisoloneDrug

    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.

  • VincristineDrug

    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.

Study groups in NCT03817853
Study groupRoleWhat they receive
Obinutuzumab+ChemotherapyExperimentalParticipants 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.
Receives: Drug: Obinutuzumab; Drug: Bendamustine; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone/Prednisolone/Methylprednisolone; Drug: Vincristine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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.

    Measured: Baseline up to end of study (approximately 4 years)

  2. 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.

    Measured: 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)

  3. 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.

    Measured: From infusion to onset of IRR during Cycle 2 (1 cycle: 21 or 28 days depending on the chemotherapy selected)

  4. 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.

    Measured: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)

  5. Type of Grade >=3 IRRs Associated With the Obinutuzumab Administered as an SDI by Cycle

    Measured: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)

  6. 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.

    Measured: All cycles including maintenance (1 cycle: 21 or 28 days depending on the chemotherapy selected; up to approximately 2.5 years)

  7. 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.

    Measured: Baseline up to end of induction therapy (up to approximately 6 months)

  8. 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.

    Measured: Baseline up to end of study (up to approximately 4 years)

  9. 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.

    Measured: Baseline up to end of study (up to approximately 4 years)

  10. 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.

    Measured: Baseline up to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2019
  2. Study start26 Feb 2019
  3. Primary completion4 Aug 2020
  4. Study completion25 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
114 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03817853
Sponsor's protocol ID
MO40597
Other IDs
2018-003255-38, 2018
Status last verified
Mar 2024
First submitted
24 Jan 2019
Last updated
4 Apr 2024
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Obinutuzumab, Bendamustine and Cyclophosphamide in people with Advanced Follicular Lymphoma, run by Hoffmann-La Roche at 33 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Germany, Japan, Spain, Brazil and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03817853.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2024.

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