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

Purpose

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.

Condition

  • Diffuse Large B-Cell Lymphoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically confirmed DLBCL, not otherwise specified (NOS) - R/R disease, defined as: relapsed = disease that has recurred following a response that 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 of the 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 candidate for high-dose chemotherapy followed by autologous stem cell transplant (ASCT) - At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or one bi-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 Criteria

  • Prior enrollment in Study GO41943 (NCT04313608), GO41944 (STARGLO; NCT04408638), or Study GO44900 (NCT06624085) - Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation - History of transformation of indolent disease to DLBCL - High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-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 murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products - Contraindication to obinutuzumab, gemcitabine or oxaliplatin, or tocilizumab - Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3 - Prior treatment with gemcitabine or oxaliplatin - Peripheral neuropathy or paresthesia assessed to be Grade >/= 2 according to the National 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 weeks prior to first study treatment - Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment - Primary or secondary CNS lymphoma at the time of recruitment or history of central nervous system (CNS) lymphoma - Prior CNS involvement that has been definitively treated and confirmed via magnetic resonance imaging (MRI) or cerebrospinal fluid analysis to be in complete remission is permissible - Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative 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 pulmonary disease) - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment - Positive for: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); tuberculosis; hepatitis B virus (HBV); hepatitis C virus (HCV); chronic active Epstein-Barr viral infection - Known or suspected history of hemophagocytic lymphohistiocytosis (HLH) or progressive multifocal leukoencephalopathy - Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia) - Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be 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 not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents), within 4 weeks prior to first dose of study treatment - Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the participant at increased risk of steroid-related iatrogenic adrenal insufficiency - Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis - Clinically significant history of cirrhotic liver disease - Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high-risk from treatment complications - Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 18 months after the final dose of study treatment

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
R/R DLBCL 		Participants with R/R DLBCL will receive obinutuzumab pre-treatment, followed by glofitamab + gemcitabine + oxaliplatin, followed by glofitamab monotherapy.
  • Drug: Obinutuzumab
    Participants will receive intravenous (IV) obinutuzumab 7 days prior to the first dose of glofitamab.
  • Drug: Glofitamab
    Participants will receive IV glofitamab, both in combination with gemcitabine and oxaliplatin and as monotherapy, for up to 12 cycles (cycle length = 21 days).
  • Drug: Gemcitabine
    Participants will receive IV gemcitabine in combination with glofitamab and oxaliplatin for up to 8 cycles (cycles length = 21 days).
  • Drug: Oxaliplatin
    Participants will receive IV oxaliplatin in combination with glofitamab and gemcitabine for up to 8 cycles (cycle length = 21 days).

Recruiting Locations

Alaska Oncology & Hematology, LLC
Anchorage, Alaska 99508

Valkyrie Clinical Trials
Los Angeles, California 90067

Nebraska Cancer Specialists
Omaha, Nebraska 68130

New York Oncology Hematology, P.C.
Albany, New York 12206

More Details

NCT ID
NCT06806033
Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO45434 https://forpatients.roche.com/
888-662-6728
global-roche-genentech-trials@gene.com

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Vanderbilt University Medical Center