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AzTrials

B-Cell LymphomaPhase 1NCT03467373

A Study of Glofitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Non-Hodgkin Lymphomas or With DLBCL

A Phase 1 study testing Glofitamab, Obinutuzumab (G) and Rituximab (R) in people with B-Cell Lymphoma and Non-Hodgkin Lymphoma, run by Hoffmann-La Roche at 22 sites in 9 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 is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
B-Cell Lymphoma, Non-Hodgkin Lymphoma
What is being tested?
Glofitamab, Obinutuzumab (G) and Rituximab (R)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
22 sitesin 9 countries
Study dates
13 Mar 2018to 2 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Age >/=18 years
  • For Part I r/r NHL dose-escalation, and Part II r/r NHL expansion: Histologically-confirmed NHL that is expected to express CD20, and which has relapsed/progressed following at least one prior treatment regimen containing R or G. Participants must be appropriate for treatment with CHOP and typically should not have been exposed to prior anthracyclines or must not exceed the cumulative lifetime dose of anthracyclines
  • For Part II untreated DLBCL expansion: Histologically confirmed previously-untreated DLBCL that is expected to express CD20
  • Able to provide a pretreatment biopsy between the final dose of last prior therapy and initiation of study medication at Cycle 1/Day 1
  • Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as >1.0 cm in its longest dimension.
  • Participants must have at least one measurable target lesion (> or = 1.5 cm) in its largest dimension by computed tomography (CT) scan
Show all 14Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for participants with r/r NHL; ECOG performance status 0-3 for participants with untreated DLBCL
  • Life expectancy (in the opinion of the Investigator) of 18 weeks
  • Adverse events (AEs) from prior anti-cancer therapy must have resolved to Grade </= 1
  • Adequate liver function
  • Adequate hematological function
  • Adequate renal function
  • Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
  • Negative test results for hepatitis C virus (HCV) and human immunodeficiency virus (HIV)

Who cannot join

  • Inability to comply with protocol mandated hospitalization and restrictions
  • Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral (including, but not limited to Epstein Barr virus (EBV), cytomegalovirus (CMV), HBV, HCV, and HIV), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics, this pertains to completion of last course of antibiotic treatment) within 4 weeks of dosing
  • Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radioimmuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal antibodies (e.g., anti-CTLA4, anti-PD1, and anti-PDL1) within 4 weeks or five half-lives of the drug, whichever is shorter, before G- or R-CHOP or Pola-R-CHP infusion on Cycle 1/Day 1
  • Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease (only for participants treated in the polatuzumab vedotin arm)
  • History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents, as follows: Grade >/=3 AEs, with the exception of Grade 3 endocrinopathy managed with replacement therapy; Grade 1-2 AEs that did not resolve to baseline after treatment completion
  • Contraindication to any of the individual components of the immunochemotherapy
Show all 26Show fewer
  • Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 4 weeks prior to study treatment at Cycle 1/Day 1 infusion
  • Prior solid organ transplantation
  • Prior allogeneic stem cell transplantation
  • Autologous stem cell transplantation within 100 days prior to Cycle 1/Day 1
  • Prior treatment with CAR T-cell therapy within 30 days prior to study treatment at Cycle 1 Day 1
  • History of autoimmune disease
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  • A history of confirmed progressive multifocal leukoencephalopathy
  • Current or past history of central nervous system (CNS) lymphoma
  • Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with </=30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle 1/Day 1. Participants may have received a brief (<7 days) course of systemic steroids (</=100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
  • Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease), and known autoimmune diseases
  • Major surgery or significant traumatic injury < 28 days prior to the study treatment infusion at Cycle 1/Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Participants with another invasive malignancy that could affect compliance with the protocol or interpretation of results
  • Significant or extensive cardiovascular disease
  • Left ventricular ejection fraction < 50%
  • Administration of a live, attenuated vaccine within 4 weeks before study treatment infusion on Cycle 1 Day 1 or anticipation that such a live, attenuated vaccine will be required during the study
  • History of illicit drug or alcohol abuse within 12 months prior to screening, in the Investigator's judgment
  • Any other diseases, metabolic dysfunction, physical examination finding (including mental status), or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Participants with latent or active tuberculosis

Trial locations and contacts

22 sites in 9 countries.

22 sites in 9 countries

Germany4 sites

  • Universitätsklinikum Erlangen, Translational Research Center (TRC), Medizin 5

    Erlangen, 91054

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

Italy4 sites

  • Asst Papa Giovanni Xxiii

    Bergamo, Lombardy, 24127

  • Istituto Nazionale Tumori Irccs Fondazione g. Pascale

    Naples, Campania, 80131

  • UO Ematologia, Ospedale S.Maria delle Croci

    Ravenna, Emilia-Romagna, 48121

  • Istituto Clinico Humanitas

    Rozzano, Lombardy, 20089

Other trials in Italy

United States3 sites

  • University of Alabama Medical Center

    Birmingham, Alabama, 35294

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Fox Chase-Temple Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

France3 sites

  • Hopital Claude Huriez

    Lille, 59037

  • Hopital Hotel Dieu Et Hme

    Nantes, 44093

  • Centre Henri Becquerel

    Rouen, 76038

Other trials in France

Spain3 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clínic i Provincial

    Barcelona, 08036

  • START Madrid-FJD, Hospital Fundacion Jimenez Diaz

    Madrid, 28040

Other trials in Spain

United Kingdom2 sites

  • University College London Hospitals NHS Foundation Trust

    London, W1T 7HA

  • Nottingham University Hospitals NHS Trust - City Hospital

    Nottingham, NG5 1PB

Other trials in United Kingdom

Australia1 site

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, 3000

Other trials in Australia

Canada1 site

  • Princess Margaret Cancer Center

    Toronto, Ontario, M5G 1Z5

Other trials in Canada

Denmark1 site

  • Rigshospitalet

    København Ø, 2100

Other trials in Denmark

About this study

Official title: A Phase Ib Study Evaluating Glofitamab (RO7082859) in Combination With Rituximab (R) or Obinutuzumab (G) Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP), or Polatuzumab Vedotin (POLA) Plus Rituximab (R), Cyclophosphamide, Doxorubicin, and Prednisone (CHP) in Participants With Relapsed or Refractory Non-Hodgkin Lymphoma (R/R NHL) or in Participants With Untreated Diffuse Large B-Cell Lymphoma (DLBCL)

This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts:

  • Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1
  • Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or OBD) will be further assessed in participants with untreated DLBCL (>18 years of age with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be studied in combination with R-CHOP and Pola-R-CHP.
Being tested
Glofitamab, Obinutuzumab (G), Rituximab (R), Tocilizumab, Cyclophosphamide
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Non-Hodgkin

What participants receive

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

  • GlofitamabDrug

    Also called RO7082859

    Glofitamab will be administered intravenously (IV) as a step-up dose for Cycle 2 on Days 8 and 15, and as a single dose from Cycle 3 onwards.

  • Obinutuzumab (G)Drug

    Also called Gazyva

    Obinutuzumab 1000 mg single dose IV infusion on Day 1 of Cycle 1 only

  • Rituximab (R)Drug

    Also called Rituxan

    Rituximab will be administered as an IV infusion at a dose of 375 mg/m^2 on Day 1 of each 21-day cycle starting from Cycle 1 to Cycle 6 (Part 1) or from Cycles 1-6 (up to 8) (Part 2: DLBCL R-CHOP).

  • TocilizumabDrug

    Also called Actemra

    Tocilizumab will be administered as an IV infusion as per the methods described in the Summary of Product Characteristics (SmPC) or other similar local prescribing documents. Tocilizumab will be given as rescue medication.

  • CyclophosphamideDrug

    Cyclophosphamide 750 mg/m^2 administered IV on Day 1 of each 21-day cycle

  • DoxorubicinDrug

    Doxorubicin 50 mg/m^2 administered IV on Day 1 of each 21-day cycle

  • VincristineDrug

    Also called Oncovin

    Vincristine 1.4 mg/m^2 administered by IV push on Day 1 of each 21-day cycle with a recommended cap of 2 mg

  • PrednisoneDrug

    Prednisone 100 mg/day orally on Days 1-5 (prednisone on Day 1 may be administered IV, with the remaining doses on Days 2-5 to be administered orally) of each 21-day cycle

  • Polatuzumab vedotinDrug

    Polatuzumab vedotin 1.8 mg/kg administered IV on Day 1 of each 21-day cycle

Study groups in NCT03467373
Study groupRoleWhat they receive
Part 1: Dose Escalation r/r NHLExperimentalDose finding in participants with r/r NHL: the study will explore different doses of glofitamab in the induction period, starting at a dose of 70 mcg administered in combination with standard of care doses of G/R CHOP and R-CHOP every 3 weeks (Q3W). Participants with r/r NHL will receive 6 cycles of induction treatment (G/R-CHOP). Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) at the end of induction (EOInd) may optionally receive post-induction treatment (referred to as maintenance) with glofitamab alone. The use of G versus R in Cycle 1 will be compared in parallel dose escalation cohorts.
Receives: Drug: Glofitamab; Drug: Obinutuzumab (G); Drug: Rituximab (R); Drug: Tocilizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone
Part 2: DLBCL G/R-CHOPExperimentalParticipants with untreated DLBCL will receive G-CHOP or R-CHOP in Cycle 1, followed by G/R-CHOP + glofitamab for subsequent cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6 (up to 8). The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.
Receives: Drug: Glofitamab; Drug: Obinutuzumab (G); Drug: Rituximab (R); Drug: Tocilizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone
Part 2: DLBCL Pola-R-CHPExperimentalParticipants with untreated DLBCL will receive Pola-R-CHP + glofitamab on Day 1 of each 21-day cycle for a maximum of 6 cycles. Glofitamab will be administered using step-up dosing for Cycle 2 on Days 8 and 15, followed by single doses on Day 8 for Cycles 3-6. The starting dose of glofitamab for each arm may be one or more levels below the MTD/OBD determined in Part I.
Receives: Drug: Glofitamab; Drug: Rituximab (R); Drug: Tocilizumab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Polatuzumab vedotin

What is being measured

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

  1. Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs)

    Measured: Up to 29 months

  2. Part I and II: Percentage of Participants with Adverse Events

    Measured: Up to 29 months

Secondary outcomes (13)

  1. Parts I and II: Percentage of Participants with a Complete Response (CR) as Assessed by the Investigator using Modified Lugano 2014 Criteria

    Measured: Up to 29 months

  2. Parts I and II: Percentage of Participants with Overall Response (Partial Response [PR] or Complete Response [CR])

    Measured: Up to 29 months

  3. Parts I and II: Duration of Response (DOR)

    Measured: Up to 29 months

  4. Duration of CR

    Measured: Up to 29 months

  5. Progression-Free Survival (PFS)

    Measured: Up to 29 months

  6. Overall Survival (OS)

    Measured: Up to 29 months

  7. Time to First Complete Response (TFCR)

    Measured: Up to 29 months

  8. Time to First Response (TFOR)

    Measured: Up to 29 months

  9. Parts I and II: Area Under the Serum Concentration Versus Time Curve (AUC) of Glofitamab

    Measured: Cycle 1 Day 1 up to 29 months

  10. Parts I and II: Time to Maximum Serum Concentration (tmax) of Glofitamab

    Measured: Cycle 1 Day 1 up to 29 months

  11. Parts I and II: Maximum Serum Concentration (Cmax) of Glofitamab

    Measured: Cycle 1 Day 1 up to 29 months

  12. Parts I and II: Minimum Serum Concentration (Cmin) of Glofitamab

    Measured: Cycle 1 Day 1 up to 29 months

  13. Change from Baseline in T-cell Activation Markers

    Measured: Up to 29 months

Timeline

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

  1. First posted16 Mar 2018
  2. Study start13 Mar 2018
  3. Primary completion2 Dec 2024
  4. Study completion2 Dec 2024

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03467373
Sponsor's protocol ID
NP40126
Other IDs
2017-003648-18, 2017
Status last verified
Jan 2025
First submitted
9 Mar 2018
Last updated
17 Jan 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Sam J, Leclercq-Cohen G, Gebhardt S, Surowka M, Herter S, Lechner K, Relf J, Briner S, Varol A, Appelt B, Domocos I, Nicolini V, Bez M, Bommer E, Jenni S, Schoenle A, Le Clech M, Colombetti S, Klein C, Umana P, Lundberg P, Korfi K, Bottos A, Bacac M. Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma. Blood. 2025 Oct 9;146(15):1824-1836. doi: 10.1182/blood.2025028863.

    PubMed 40749164

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Glofitamab, Obinutuzumab (G) and Rituximab (R) in people with B-Cell Lymphoma and Non-Hodgkin Lymphoma, run by Hoffmann-La Roche at 22 sites in 9 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 14 inclusion and 26 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 17 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Germany, Italy, United States, France, Spain and 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Part I: Percentage of Participants with Dose Limiting Toxicities (DLTs) (time frame: Up to 29 months). The study lists 2 primary outcomes in all. 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 NCT03467373, which also lists 1 linked publication.

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 17 Jan 2025.

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