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RecruitingInterventionalPhase 2

A Phase II, Open-Label, Multicenter Study to Evaluate the Optimization of the Cytokine Release Syndrome Profile for Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in Patients With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma

NCT ID: NCT06806033Sponsor: Hoffmann-La RocheLast updated: 2026-05-26

Summary

This Phase II trial evaluates the optimization of the cytokine release syndrome (CRS) profile for glofitamab in combination with gemcitabine and oxaliplatin (Glofit-GemOx) in participants with relapsed or refractory aggressive B-cell Non-Hodgkin's lymphoma. The study utilizes an optimized steroid premedication regimen and monitoring schedule specifically designed to enable the administration of the treatment regimen in an outpatient setting.

Arms & interventions

  • DrugObinutuzumab

    Participants will receive intravenous (IV) obinutuzumab 7 days prior to the first dose of glofitamab.

  • DrugGlofitamab

    Participants will receive IV glofitamab, both in combination with gemcitabine and oxaliplatin and as monotherapy, for up to 12 cycles (cycle length = 21 days).

  • DrugGemcitabine

    Participants will receive IV gemcitabine in combination with glofitamab and oxaliplatin for up to 8 cycles (cycles length = 21 days).

  • DrugOxaliplatin

    Participants will receive IV oxaliplatin in combination with glofitamab and gemcitabine for up to 8 cycles (cycle length = 21 days).

Outcome measures

Primary

  • Incidence of cytokine release syndrome (CRS)

    Time frame: Up to approximately 5 years

Secondary

  • Incidence of serious cytokine release syndrome (CRS) events

    Time frame: Up to approximately 5 years

  • CRS frequency relative to the start of glofitamab infusions

    Time frame: Up to approximately 5 years

  • Complete response (CR) rate as determined by independent review facility (IRF) and the investigator

    Time frame: Up to approximately 5 years

  • Overall response rate (ORR) as determined by IRF and the investigator

    Time frame: Up to approximately 5 years

  • Duration of response (DOR)

    Time frame: From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)

  • Duration of complete response (DOCR)

    Time frame: From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)

  • Progression-free survival (PFS) as determined by the IRF and the investigator

    Time frame: From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)

  • Overall survival (OS)

    Time frame: From enrollment to date of death from any cause (Up to approximately 5 years)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: * Histologically confirmed large B-cell lymphoma (de novo or transformed from FL) with one of the following diagnoses according to World Health Organization, fifth edition: DLBCL Not Otherwise Specified (NOS); High-Grade B-Cell Lymphoma (HGBL), NOS; DLBCL/HGBL with MYC and BCL2 rearrangements * 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 * According to the investigator's judgment, participants should be able to receive the step-up dose regimen in an outpatient setting * Adequate hematologic and renal function Exclusion Criteria: * Prior enrollment in Studies 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 * Any history of Waldenstrom's macroglobulinemia * 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 * 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 locations (33)

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, 99508

Recruiting

Community Cancer Institute (CCI)

Clovis, California, 93611

Recruiting

Providence Medical Foundation

Fullerton, California, 92835

Recruiting

Los Angeles Cancer Network

Glendale, California, 91204

Recruiting

Valkyrie Clinical Trials

Los Angeles, California, 90067

Recruiting

Valkyrie Clinical Trials

Panorama City, California, 91402

Recruiting

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110

Recruiting

The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente

Torrance, California, 90502-2006

Recruiting

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, 80012

Recruiting

North Florida/ South Georgia VA Medical Center

Gainesville, Florida, 32608

Recruiting

Mount Sinai Comprehensive Cancer Center

Miami, Florida, 33140

Recruiting

Orlando Health Cancer Institute

Orlando, Florida, 32806

Recruiting

St Luke?s Cancer Institute

Boise, Idaho, 83712

Recruiting

Cancer Care Specialists of Central Illinois

Swansea, Illinois, 62226

Recruiting

Mission Blood and Cancer - MercyOne Cancer Center

Waukee, Iowa, 50263

Recruiting

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536

Recruiting

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana, 70809

Recruiting

Boston Medical Center

Boston, Massachusetts, 02118

Recruiting

Corewell Health

Grand Rapids, Michigan, 49503

Recruiting

Nebraska Cancer Specialists

Omaha, Nebraska, 68130

Recruiting

New York Oncology Hematology, P.C.

Albany, New York, 12206

Recruiting

Hematology Oncology Associates of Central New York

East Syracuse, New York, 13057

Recruiting

Oncology Associates of Oregon, P.C

Eugene, Oregon, 97401

Recruiting

Providence Portland Medical Center

Portland, Oregon, 97213

Recruiting

Providence St. Vincent Medical Center

Portland, Oregon, 97225

Recruiting

Tennessee Oncology

Chattanooga, Tennessee, 37403

Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Recruiting

Baylor Scott & White Health

Temple, Texas, 76502

Recruiting

Texas Oncology - Gulf Coast

The Woodlands, Texas, 77380

Recruiting

Texas Oncology- Northeast Texas

Tyler, Texas, 75702

Recruiting

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031

Recruiting

Virginia Oncology Associates - Virginia Beach

Virginia Beach, Virginia, 23456

Recruiting

Northwest Medical Specialties

Tacoma, Washington, 98405

Recruiting