A Study to Evaluate the Optimization of the Cytokine Release Syndrome Profile for Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Last updated: April 18, 2025
Sponsor: Hoffmann-La Roche
Overall Status: Active - Recruiting

Phase

2

Condition

Hematologic Cancer

Lymphoma

Lymphoma, B-cell

Treatment

Obinutuzumab

Gemcitabine

Glofitamab

Clinical Study ID

NCT06806033
GO45434
  • Ages > 18
  • All Genders

Study Summary

The main goal of this trial is to study the frequency and severity of cytokine release syndrome (CRS) in participants with diffuse large B-cell lymphoma (DLBCL) who are using a combination of glofitamab + gemcitabine + oxaliplatin (Glofit-GemOx) followed by glofitamab-only treatment.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Histologically confirmed DLBCL, not otherwise specified (NOS)

  • R/R disease, defined as: relapsed = disease that has recurred following a responsethat lasted >/= 6 months after completion of the last line of therapy; refractory =disease that did not respond to or that progressed < 6 months after completion ofthe last line of therapy

  • At least one line of prior systemic therapy

  • Participants who have failed only one prior line of therapy must not be a candidatefor high-dose chemotherapy followed by autologous stem cell transplant (ASCT)

  • At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or onebi-dimensionally measurable (> 1 cm) extranodal lesion, as measured on CT scan

  • Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2

  • Adequate hematologic and renal function

Exclusion

Exclusion Criteria:

  • Prior enrollment in Study GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), orStudy GO44900 (NCT06624085)

  • Participant has failed only one prior line of therapy and is a candidate for stemcell transplantation

  • History of transformation of indolent disease to DLBCL

  • High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, andhigh-grade B-cell lymphoma NOS, as defined by 2016 WHO guidelines

  • Primary mediastinal B-cell lymphoma

  • History of severe allergic or anaphylactic reactions to humanized or murinemonoclonal antibodies (or recombinant antibody-related fusion proteins) or knownsensitivity or allergy to murine products

  • Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab

  • Prior treatment with glofitamab or other bispecific antibodies targeting both CD20and CD3

  • Prior treatment with gemcitabine or oxaliplatin

  • Peripheral neuropathy or paresthesia assessed to be Grade >/= 2 according to theNational Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)v5.0 at enrollment

  • Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy,or any investigational agent for the purposes of treating cancer within 2 weeksprior to first study treatment

  • Treatment with monoclonal antibodies for the purposes of treating cancer within 4weeks prior to first study treatment

  • Primary or secondary CNS lymphoma at the time of recruitment or history of centralnervous system (CNS) lymphoma

  • Prior CNS involvement that has been definitively treated and confirmed via magneticresonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remissionis permissible

  • Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, orneurodegenerative disease

  • History of other primary malignancy, with exceptions defined by the protocol

  • Significant or extensive cardiovascular disease

  • Significant pulmonary disease (including moderate or severe obstructive pulmonarydisease)

  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episodeof infection (as evaluated by the investigator) within 4 weeks prior to the firststudy treatment

  • Positive for: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2);tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); chronic activeEpstein-Barr viral infection

  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) orprogressive multifocal leukoencephalopathy

  • Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 orbetter (with the exception of alopecia and anorexia)

  • Administration of a live, attenuated vaccine within 4 weeks before first studytreatment administration or anticipation that such a live, attenuated vaccine willbe required during the study

  • Prior solid organ transplantation or prior allogenic stem cell transplant

  • Active autoimmune disease requiring treatment

  • Prior treatment with systemic immunosuppressive medications (including, but notlimited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumornecrosis factor agents), within 4 weeks prior to first dose of study treatment

  • Ongoing systemic corticosteroid use which, in the opinion of the investigator, putsthe participant at increased risk of steroid-related iatrogenic adrenalinsufficiency

  • Recent major surgery (within 4 weeks before the first study treatment) other thanfor diagnosis

  • Clinically significant history of cirrhotic liver disease

  • Any other diseases, metabolic dysfunction, physical examination finding, or clinicallaboratory finding giving reasonable suspicion of a disease or condition thatcontraindicates the use of an investigational drug or that may affect theinterpretation of the results or renders the participant at high-risk from treatmentcomplications

  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study orwithin 18 months after the final dose of study treatment

Study Design

Total Participants: 100
Treatment Group(s): 4
Primary Treatment: Obinutuzumab
Phase: 2
Study Start date:
March 05, 2025
Estimated Completion Date:
March 31, 2029

Connect with a study center

  • Arthur J.E. Child Comprehensive Cancer Center

    Calgary, Alberta T2N 5G2
    Canada

    Active - Recruiting

  • CancerCare Manitoba

    Winnipeg, Manitoba R3E 0V9
    Canada

    Active - Recruiting

  • CancerCare Manitoba (CCMB)

    Winnipeg, Manitoba R3E 0V9
    Canada

    Active - Recruiting

  • CHU de Bordeaux

    Pessac, 33600
    France

    Active - Recruiting

  • Istituto Clinico Humanitas

    Rozzano, Lombardia 20089
    Italy

    Active - Recruiting

  • Seoul National University Bundang Hospital

    Seongnam-si, 463-707
    Korea, Republic of

    Active - Recruiting

  • Asan Medical Center

    Seoul, 05505
    Korea, Republic of

    Active - Recruiting

  • Alaska Oncology & Hematology, LLC

    Anchorage, Alaska 99508
    United States

    Active - Recruiting

  • Valkyrie Clinical Trials

    Los Angeles, California 90067
    United States

    Active - Recruiting

  • Nebraska Cancer Specialists

    Omaha, Nebraska 68130
    United States

    Active - Recruiting

  • New York Oncology Hematology, P.C.

    Albany, New York 12206
    United States

    Active - Recruiting

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