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CompletedNCT04703686Updated Mar 16, 2026

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

A Phase 2 interventional study of Obinutuzumab and RO7082859 in Diffuse Large B-Cell Lymphoma Refractory, Refractory Indolent Adult Non-Hodgkin Lymphoma and Refractory Transformed B-cell Non-Hodgkin Lymphoma, sponsored by The Lymphoma Academic Research Organisation. Completed at 19 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-16.

Sponsored by The Lymphoma Academic Research Organisation · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
67
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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 PET-CT central review allowing inclusion in this trial.

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

02

Conditions studied

  • Diffuse Large B-Cell Lymphoma Refractory
  • Refractory Indolent Adult Non-Hodgkin Lymphoma
  • Refractory Transformed B-cell Non-Hodgkin Lymphoma
  • Refractory Primary Mediastinal Large B-Cell Cell Lymphoma
  • Refractory Mantle Cell Lymphoma

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Keywords

  • Post Car T-cells therapy
03

In context

Lymphoma, Mantle-Cell

783 studies on the registry are indexed under Lymphoma, Mantle-Cell; 146 are open to participants now.

This study's enrollment of 67 is above the median of 39 across 699 interventional studies indexed under Lymphoma, Mantle-Cell.

Browse Lymphoma, Mantle-Cell studies →

Lead sponsor

The Lymphoma Academic Research Organisation is the lead sponsor of 60 studies on the registry; 12 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. 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
  2. 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)
  3. First metabolic progression, first relapse or no metabolic response after CAR T-cells infusion must be confirmed by PET-CT central review for enrollment
  4. DLBCL with demonstrated lymphoma cells-expressing CD20 at relapse post CAR T-cells as demonstrated by biopsy before enrollment (cohort 1 only)
  5. Aged 18 years or more with no upper age limit
  6. ECOG performance status 0 or 1
  7. 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
  8. No persistant CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of neurotoxicity grade > 3
  9. Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted)
  10. 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)
  11. 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
  12. Adequate renal function: creatinine clearance (CrCl) calculated by MDRD/cockcroft -Gault formula of ≥ 30 mL/min
  13. Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential
  14. 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
  15. 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

  16. 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
  17. 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.
  18. Signed written informed consent
  19. Life expectancy ≥ 3 months
  20. Patient covered by any social security system
  21. Patient who understands and speaks one of the country official languages

Exclusion criteria

Exclusion Criteria:

  1. 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
  2. Patients with CLL, Richter and Burkitt lymphoma
  3. Patients relapsing or progressing within 1 months (30 days) after CAR T-cells therapy

  4. 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
  5. Current or past history of detectable cerebrospinal fluid lymphoma cells, or with a history of CNS lymphoma localization or primary CNS lymphoma
  6. Current or past history of cerebral disorders
  7. Any serious psychiatric illness that would prevent the subject from signing the informed consent form.
  8. Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH)
  9. 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
  10. 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)
  11. Any serious active disease or co-morbid medical condition
  12. Clinically significant history of liver disease or cirrhosis
  13. 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
  14. Prior solid organ transplantation
  15. Prior allogeneic SCT
  16. Autologous SCT within 100 days prior to obinutuzumab infusion
  17. Current uncontrolled autoimmune disease Note: History of autoimmune disease currently controlled and stable is acceptable for such therapy. See detailed description below*
  18. 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
  19. 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
  20. Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion
  21. 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
  22. Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
  23. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
  24. History of illicit drug or alcohol abuse within 12 months prior to enrollment
  25. Person deprived of his/her liberty by a judicial or administrative decision
  26. Inability to comply with protocol mandated hospitalization and restrictions
  27. Adult person under legal protection
  28. Adult person unable to provide informed consent because of intellectual impairment, any serious medical condition, laboratory abnormality or psychiatric illness
  29. Pregnant or breast-feeding or intending to become pregnant during the study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
67 participants (actual)

Study arms

  • Experimental
    Obinutuzumab + RO7082859

    Drug: Obinutuzumab · Drug: RO7082859

Interventions

  • DrugObinutuzumab

    1000mg - prephase - one infusion at D-3

    Also known as: gazyva

  • DrugRO7082859

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

    Also known as: glofitamab

06

What researchers measure

Primary outcomes

  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

    Time frame: 4 years

Secondary outcomes

  1. Metabolic response rates according to Lugano classification

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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),

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

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

  29. number of Serious Adverse Events

    Time frame: 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

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

  31. Best metabolic response assessed by central review

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

07

Study locations

19 sites
  • CHU Amiens Picardie Site sud
    Amiens, France
  • CHU de Clermont Ferrand
    Clermont-Ferrand, 63000, France
  • Hopital Henri Mondor
    Créteil, 94010, France
  • CHU de Dijon - Hôpital le Bocage
    Dijon, 21034, France
  • CHU de Grenoble
    Grenoble, 38043, France
  • CHRU Lille - Hôpital Claude Huriez
    Lille, 59037, France
  • CHU Montpellier
    Montpellier, 34295, France
  • CHU Nantes
    Nantes, 44093, France
  • Hôpital Saint Louis
    Paris, 75475, France
  • Hopital Necker enfants malades
    Paris, 7574, France
  • APHP - Hôpital de la Pitiè Salpetrière
    Paris, France
  • APHP - Hôpital Saint Antoine
    Paris, France
  • CHU de Bordeaux - Hôpital Haut Leveque
    Pessac, 33604, France
  • CHU Lyon Sud
    Pierre-Bénite, 69130, France
  • CHU de Rennes - Hôpital Pontchaillou
    Rennes, 35033, France
  • Centre Henri Becquerel
    Rouen, 76038, France
  • IUCT Oncopole
    Toulouse, 31059, France
  • CHU Tours Hopital Bretonneau
    Tours, 37044, France
  • CHU de Brabois
    Vandœuvre-lès-Nancy, France
08

References and documents

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 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 16, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04703686
Lead sponsor
The Lymphoma Academic Research Organisation
Responsible party
Sponsor
First posted
Jan 11, 2021
Start date
Mar 30, 2021
Primary completion
Jan 10, 2023
Completion
May 21, 2025
Last update
Mar 16, 2026

Study contacts

Guillaume Cartron, MD,PhD
study chair · Lymphoma Study Association
Pierre Sesques, MD
study chair · Lymphoma Study Association

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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