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Diffuse Large B-Cell Lymphoma RefractoryPhase 2NCT04703686

Treatment by a Bispecific CD3xCD20 Antibody for Relapse/Refractory Lymphomas After CAR T-cells Therapy

A Phase 2 study testing Obinutuzumab and RO7082859 in people with Diffuse Large B-Cell Lymphoma Refractory and Refractory Indolent Adult Non-Hodgkin Lymphoma, run by The Lymphoma Academic Research Organisation at 19 sites in France.

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 study is a multicenter phase II trial including 2 cohorts of patients in Refractory/Relapse disease at least 1 month after CAR T-cells therapy: cohort 1: DLBCL patients cohort 2: PMBL, mantle cell lymphoma, transformed indolent NHL (t-iNHL) or iNHL CAR T-cells Refractory/Relapse status will be determined by… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Obinutuzumab and RO7082859
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
19 sitesFrance
Study dates
30 Mar 2021to 21 May 2025
Phase
Phase 2
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

  • Patients who received CAR T-cells therapy for R/R DLBCL (cohort 1) or R/R PMBL, mantle cell lymphoma, t-iNHL or iNHL (cohort 2), at least 1 month ago
  • Patients who are not, at least in partial metabolic response from 1 month after CAR T-cells infusion (i.e no metabolic response or first metabolic progressive disease or first relapse from 1 month after CAR T-cells infusion)
  • First metabolic progression, first relapse or no metabolic response after CAR T-cells infusion must be confirmed by PET-CT central review for enrollment
  • DLBCL with demonstrated lymphoma cells-expressing CD20 at relapse post CAR T-cells as demonstrated by biopsy before enrollment (cohort 1 only)
  • Aged 18 years or more with no upper age limit
  • ECOG performance status 0 or 1
Show all 23Show fewer
  • Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan, or PET-CT with at least one hypermetabolic lesion
  • No persistant CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of neurotoxicity grade > 3
  • Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted)
  • Adequate liver function: Total bilirubin ≤ 1.5 x ULN; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN Note: Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible)
  • Adequate hematological function: Neutrophil count of ≥ 1.0 G/L; Platelet count of ≥ 50 G/L (and platelet transfusion free within 14 days prior to administration of obinutuzumab); Hemoglobin (Hb) ≥ 8.0 g/dL (transfusion free within 21 days prior to administration of obinutuzumab) Note: patients who do not meet the above hematologic criteria, due to extensive tumor involvement in the marrow may be enrolled into the trial after the demonstration of involvement and consultation with the LYSARC. Please consult the LYSARC on the need for transfusion support within 21 days of obinutuzumab
  • Adequate renal function: creatinine clearance (CrCl) calculated by MDRD/cockcroft -Gault formula of ≥ 30 mL/min
  • Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential
  • Negative serologic or PCR test results for acute or chronic HBV infection Note: Patients whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation
  • Negative test results for HCV and HIV Note: Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation
  • Patients must agree to either remain completely abstinent or to use two effective contraceptive methods* until:
  • If the patient is a male: at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer, Men must refrain from donating sperm during this same period
  • If patient is a female of childbearing potential: until at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer
  • Patient must be willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of glofitamab. Patient must also be willing to comply with all study-related procedures.
  • Signed written informed consent
  • Life expectancy ≥ 3 months
  • Patient covered by any social security system
  • Patient who understands and speaks one of the country official languages

Who cannot join

  • Previously known CD20 negative status, excepted if a new biopsy for cohort 1 or biopsy or cytometry analysis for cohort 2 proving a CD20 positive status is available before enrollment
  • Patients with CLL, Richter and Burkitt lymphoma
  • Patients relapsing or progressing within 1 months (30 days) after CAR T-cells therapy
  • History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
  • Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy
  • Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation
Show all 31Show fewer
  • Current or past history of detectable cerebrospinal fluid lymphoma cells, or with a history of CNS lymphoma localization or primary CNS lymphoma
  • Current or past history of cerebral disorders
  • Any serious psychiatric illness that would prevent the subject from signing the informed consent form.
  • Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH)
  • Patients with known acute infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, 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) in 2 week prior to enrollment
  • LVEF < 40% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan or significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
  • Any serious active disease or co-morbid medical condition
  • Clinically significant history of liver disease or cirrhosis
  • Prior history of malignancies other than lymphoma unless the subject has been free of the disease for ≥ 3 years. Exceptions will be allowed for patients with non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or any surgically removed stage 0 (in situ) carcinoma
  • Prior solid organ transplantation
  • Prior allogeneic SCT
  • Autologous SCT within 100 days prior to obinutuzumab infusion
  • Current uncontrolled autoimmune disease Note: History of autoimmune disease currently controlled and stable is acceptable for such therapy. See detailed description below*
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Major surgery or significant traumatic injury < 28 days prior to the obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion
  • Treatment between infusion of CAR T-cells and pre-phase (i.e. obinutuzumab infusion on C1/D-3): with standard radiotherapy, systemic immunotherapeutic agents, any chemotherapeutic agent, any systemic immunosuppressive medications or treatment with any other investigational anti-cancer agent (defined as treatment for which there is currently no regulatory authority approved indication) Note: with the exception of corticosteroid treatment < 25 mg/day prednisone or equivalent. Inhaled and topical steroids are permitted
  • Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
  • History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  • History of illicit drug or alcohol abuse within 12 months prior to enrollment
  • Person deprived of his/her liberty by a judicial or administrative decision
  • Inability to comply with protocol mandated hospitalization and restrictions
  • Adult person under legal protection
  • Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
  • Pregnant or breast-feeding or intending to become pregnant during the study

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

France19 sites

  • CHU Amiens Picardie Site sud

    Amiens

  • CHU de Clermont Ferrand

    Clermont-Ferrand, 63000

  • Hopital Henri Mondor

    Créteil, 94010

  • CHU de Dijon - Hôpital le Bocage

    Dijon, 21034

  • CHU de Grenoble

    Grenoble, 38043

  • CHRU Lille - Hôpital Claude Huriez

    Lille, 59037

  • CHU Montpellier

    Montpellier, 34295

  • CHU Nantes

    Nantes, 44093

  • Hôpital Saint Louis

    Paris, 75475

  • Hopital Necker enfants malades

    Paris, 7574

  • APHP - Hôpital de la Pitiè Salpetrière

    Paris

  • APHP - Hôpital Saint Antoine

    Paris

  • CHU de Bordeaux - Hôpital Haut Leveque

    Pessac, 33604

  • CHU Lyon Sud

    Pierre-Bénite, 69130

  • CHU de Rennes - Hôpital Pontchaillou

    Rennes, 35033

  • Centre Henri Becquerel

    Rouen, 76038

  • IUCT Oncopole

    Toulouse, 31059

  • CHU Tours Hopital Bretonneau

    Tours, 37044

  • CHU de Brabois

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: A Phase II Trial Evaluating Glofitamab, a Bispecific CD3xCD20 Antibody for Relapse/Refractory Lymphomas After CAR T-cells Therapy

This study is a multicenter phase II trial including 2 cohorts of patients in Refractory/Relapse disease at least 1 month after CAR T-cells therapy:

  • cohort 1: DLBCL patients
  • cohort 2: PMBL, mantle cell lymphoma, transformed indolent NHL (t-iNHL) or iNHL CAR T-cells Refractory/Relapse status will be determined by PET-CT central review allowing inclusion in this trial.
Read more

Patients enrolled will then receive a pre-phase of obinutuzumab followed by experimental treatment:11 cycle of glofitamab.

The primary objective of the study is to assess the anti-lymphoma activity of glofitamab, a bispecific CD3xCD20 monoclonal antibody in patients with relapse/refractory DLBCL (cohort 1) disease after anti-CD19 CAR T-cells therapy

Being tested
Obinutuzumab, RO7082859
Keywords
Post Car T-cells therapy
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

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

  • ObinutuzumabDrug

    Also called gazyva

    1000mg - prephase - one infusion at D-3

  • RO7082859Drug

    Also called glofitamab

    2.5 mg D1C1, 10 mg D3C1, then 30 mg D8C1 and D1 every 21 days (C2-C11, D1C2 starts 14 days after D1C1)

Study groups in NCT04703686
Study groupRoleWhat they receive
Obinutuzumab + RO7082859ExperimentalNot described
Receives: Drug: Obinutuzumab; Drug: RO7082859

What is being measured

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

  1. Overall Survival

    Overall survival will be measured from the date of C1D1 of glofitamab to the date of death from any cause. Alive patients will be censored at the date of last contact

    Measured: 4 years

Secondary outcomes (31)

  1. Metabolic response rates according to Lugano classification

    Response will be assessed by local and central review by PET scan according to Lugano classification

    Measured: At the end of Cycle 2 (1st cycle of 14 days and subsequent cycles of 21 days)

  2. Metabolic response rates according to Lugano classification

    Response will be assessed by local and central review by PET scan according to Lugano classification

    Measured: At the end of Cycle 6 (1st cycle of 14 days and subsequent cycles of 21 days)

  3. Metabolic response rates according to Lugano classification

    Response will be assessed by local and central review by PET scan according to Lugano classification

    Measured: At the end of Cycle 9 (1st cycle of 14 days and subsequent cycles of 21 days)

  4. Metabolic response rates according to Lugano classification

    Response will be assessed by local and central review by PET scan according to Lugano classification

    Measured: At the end of Cycle 11 (1st cycle of 14 days and subsequent cycles of 21 days)

  5. Progression Free Survival (PFS)

    PFS is defined as the time from enrollment into the study to the first observation of documented disease progression based on central review or death due to any cause

    Measured: At the end of Cycle 2 (1st cycle of 14 days and subsequent cycles of 21 days)

  6. Progression Free Survival (PFS)

    PFS is defined as the time from enrollment into the study to the first observation of documented disease progression based on central review or death due to any cause

    Measured: At the end of Cycle 4 (1st cycle of 14 days and subsequent cycles of 21 days)

  7. Progression Free Survival (PFS)

    PFS is defined as the time from enrollment into the study to the first observation of documented disease progression based on central review or death due to any cause

    Measured: At the end of Cycle 6 (1st cycle of 14 days and subsequent cycles of 21 days)

  8. Progression Free Survival (PFS)

    PFS is defined as the time from enrollment into the study to the first observation of documented disease progression based on central review or death due to any cause

    Measured: At the end of Cycle 9 (1st cycle of 14 days and subsequent cycles of 21 days)

  9. Progression Free Survival (PFS)

    PFS is defined as the time from enrollment into the study to the first observation of documented disease progression based on central review or death due to any cause

    Measured: At the end of Cycle 11 (1st cycle of 14 days and subsequent cycles of 21 days)

  10. Duration of Response (DoR)

    DoR is defined from the time of first CMR or PMR (according to Lugano criteria) to the date of first documented disease progression, relapse or death from any cause. If a subject has not progressed or died, DoR will be censored at the date of tumor assessment

    Measured: At the end of Cycle 2 (1st cycle of 14 days and subsequent cycles of 21 days)

  11. Duration of Response (DoR)

    DoR is defined from the time of first CMR or PMR (according to Lugano criteria) to the date of first documented disease progression, relapse or death from any cause. If a subject has not progressed or died, DoR will be censored at the date of tumor assessment

    Measured: At the end of Cycle 4 (1st cycle of 14 days and subsequent cycles of 21 days)

  12. Duration of Response (DoR)

    DoR is defined from the time of first CMR or PMR (according to Lugano criteria) to the date of first documented disease progression, relapse or death from any cause. If a subject has not progressed or died, DoR will be censored at the date of tumor assessment

    Measured: At the end of Cycle 6 (1st cycle of 14 days and subsequent cycles of 21 days)

  13. Duration of Response (DoR)

    DoR is defined from the time of first CMR or PMR (according to Lugano criteria) to the date of first documented disease progression, relapse or death from any cause. If a subject has not progressed or died, DoR will be censored at the date of tumor assessment

    Measured: At the end of Cycle 9 (1st cycle of 14 days and subsequent cycles of 21 days)

  14. Duration of Response (DoR)

    DoR is defined from the time of first CMR or PMR (according to Lugano criteria) to the date of first documented disease progression, relapse or death from any cause. If a subject has not progressed or died, DoR will be censored at the date of tumor assessment

    Measured: At the end of Cycle 11 (1st cycle of 14 days and subsequent cycles of 21 days)

  15. Quality of Life - QLQ-C30

    Quality of Life scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30),

    Measured: at day 1

  16. Quality of Life - FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: at day 1

  17. Quality of Life - QLQ-C30

    Quality of Life scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Measured: At Cycle 2 Day 1 (1st cycle of 14 days and subsequent cycles of 21 days)

  18. Quality of Life - FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: At Cycle 2 Day 1 (1st cycle of 14 days and subsequent cycles of 21 days)

  19. Quality of Life - EORTC QLQ-C30

    Quality of Life scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Measured: At Cycle 3 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  20. Quality of Life _ FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: At Cycle 3 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  21. Quality of Life - QLQ-C30

    Quality of Life scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Measured: At cycle 5 day 1 (1st cycle of 14 days and subsequent cycles of 21 days)

  22. Quality of Life _ FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: At cycle 5 day 1 (1st cycle of 14 days and subsequent cycles of 21 days)

  23. Quality of Life _ QLQ-C30

    Quality of Life scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Measured: At Cycle 7 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  24. Quality of Life _ FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: At Cycle 7 Day 1 (1st cycle of 14 days and subsequent cycles of 21 days)

  25. Quality of Life _ QLQ-C30

    Quality of Life scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Measured: At Cycle 9 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  26. Quality of Life _ FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: At Cycle 9 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  27. Quality of Life _ QLQ-C30

    Quality of Lifescale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

    Measured: At Cycle 11 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  28. Quality of Life _ FACT-Lym LymS

    Quality of Life scale measurements will be the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale

    Measured: At Cycle 11 Day 1(1st cycle of 14 days and subsequent cycles of 21 days)

  29. number of Serious Adverse Events

    Measured: from the date of first informed consent signature to 30 days after last administration of study drugs

  30. Best metabolic response assessed by local review

    Measured: after 11 cycles (1st cycle of 14 days and subsequent cycles of 21 days)

  31. Best metabolic response assessed by central review

    Measured: after 11 cycles (1st cycle of 14 days and subsequent cycles of 21 days)

Timeline

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

  1. First posted11 Jan 2021
  2. Study start30 Mar 2021
  3. Primary completion10 Jan 2023
  4. Study completion21 May 2025

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04703686
Sponsor's protocol ID
BiCAR
Status last verified
Mar 2026
First submitted
4 Jan 2021
Last updated
16 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Cartron G, Chaillol I, Houot R, Al Tabaa Y, Le Bras F, Ysebaert L, Choquet S, Jardin F, Bay JO, Gros FX, Morschhauser F, Rossi C, Gastinne T, Thieblemont C, Joris M, Ricard L, Regny C, La Rochelle LD, Feugier P, Marcais A, Ould-Ammar R, Tarte K, Laurent C, Sesques P. Short ramp-up glofitamab halves mortality risk after anti-CD19 CAR T-cell therapy failure in patients with diffuse large B-cell lymphoma: final results of the LYSA BiCAR phase 2 trial with a pre-specified external control arm. J Hematol Oncol. 2026 Jul 1. doi: 10.1186/s13045-026-01816-4. Online ahead of print.

    PubMed 42393723

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Obinutuzumab and RO7082859 in people with Diffuse Large B-Cell Lymphoma Refractory and Refractory Indolent Adult Non-Hodgkin Lymphoma, run by The Lymphoma Academic Research Organisation at 19 sites in France.

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 23 inclusion and 31 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 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Overall Survival (time frame: 4 years). 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 NCT04703686, 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 16 Mar 2026.

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