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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 Aggressive B-Cell Non-Hodgkin's Lymphoma

NCT06806033 · Hoffmann-La Roche
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Official title
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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 100 participants
Allocation: na
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-03-05
Estimated completion: 2029-03-30
Last updated: 2026-03-31
Interventions
Drug: ObinutuzumabDrug: GlofitamabDrug: GemcitabineDrug: Oxaliplatin
Primary outcomes
  • Incidence of cytokine release syndrome (CRS) (Up to approximately 5 years)
Sponsor
Hoffmann-La Roche · industry
Contacts & investigators
ContactReference Study ID Number: GO45434 https://forpatients.roche.com/ · contact · global-roche-genentech-trials@gene.com · 888-662-6728
InvestigatorStudy Director · study_director, Hoffmann-La Roche
All locations (51)
Alaska Oncology & Hematology, LLCRecruiting
Anchorage, Alaska, United States
Community Cancer Institute (CCI)Recruiting
Clovis, California, United States
Providence Medical FoundationRecruiting
Fullerton, California, United States
Los Angeles Cancer NetworkRecruiting
Glendale, California, United States
Valkyrie Clinical TrialsRecruiting
Los Angeles, California, United States
Zuckerberg San Francisco General HospitalRecruiting
San Francisco, California, United States
The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical CenteRecruiting
Torrance, California, United States
Rocky Mountain Cancer Centers, LLPRecruiting
Aurora, Colorado, United States
North Florida/ South Georgia VA Medical CenterRecruiting
Gainesville, Florida, United States
Mount Sinai Comprehensive Cancer CenterRecruiting
Miami, Florida, United States
Orlando Health Cancer InstituteRecruiting
Orlando, Florida, United States
St Luke?s Cancer InstituteRecruiting
Boise, Idaho, United States
Cancer Care Specialists of Central IllinoisRecruiting
Swansea, Illinois, United States
Mission Blood and Cancer - MercyOne Cancer CenterRecruiting
Waukee, Iowa, United States
University of Kentucky - Markey Cancer CenterRecruiting
Lexington, Kentucky, United States
Mary Bird Perkins Cancer CtrRecruiting
Baton Rouge, Louisiana, United States
Boston Medical CenterRecruiting
Boston, Massachusetts, United States
Nebraska Cancer SpecialistsRecruiting
Omaha, Nebraska, United States
New York Oncology Hematology, P.C.Recruiting
Albany, New York, United States
Hematology Oncology Associates of Central New YorkRecruiting
East Syracuse, New York, United States
Oncology Associates of Oregon, P.CRecruiting
Eugene, Oregon, United States
Providence Portland Medical CenterRecruiting
Portland, Oregon, United States
Providence St. Vincent Medical CenterRecruiting
Portland, Oregon, United States
Tennessee OncologyRecruiting
Chattanooga, Tennessee, United States
Tennessee OncologyRecruiting
Nashville, Tennessee, United States
Baylor Scott & White HealthRecruiting
Temple, Texas, United States
Texas Oncology - Gulf CoastRecruiting
The Woodlands, Texas, United States
Texas Oncology- Northeast TexasRecruiting
Tyler, Texas, United States
Virginia Cancer Specialists, PCRecruiting
Fairfax, Virginia, United States
Virginia Oncology Associates - Virginia BeachRecruiting
Virginia Beach, Virginia, United States
Northwest Medical SpecialtiesRecruiting
Tacoma, Washington, United States
Epworth HospitalRecruiting
East Melbourne, Victoria, Australia
Arthur J.E. Child Comprehensive Cancer CenterRecruiting
Calgary, Alberta, Canada
CancerCare Manitoba (CCMB)Recruiting
Winnipeg, Manitoba, Canada
CHU de GrenobleRecruiting
La Tronche, France
Chu de Montpellier-St EloiRecruiting
Montpellier, France
CHU de BordeauxRecruiting
Pessac, France
CHU DE RENNES - CHU PontchaillouRecruiting
Rennes, France
Chu De ToursRecruiting
Tours, France
CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.OnkologieRecruiting
Berlin, Germany
Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)Recruiting
Berlin, Germany
Universitätsklinikum KölnRecruiting
Cologne, Germany
Otto von Guericke Uni Magdeburg UniklinikRecruiting
Magdeburg, Germany
Istituto Nazionale Tumori Irccs Fondazione g. PascaleRecruiting
Naples, Campania, Italy
IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"Recruiting
Meldola, Emilia-Romagna, Italy
A.O. Spedali Civili Di Brescia-P.O. Spedali CiviliRecruiting
Brescia, Lombardy, Italy
Irccs Istituto Europeo Di Oncologia (IEO)Recruiting
Milan, Lombardy, Italy
Istituto Clinico HumanitasRecruiting
Rozzano, Lombardy, Italy
Seoul National University Bundang HospitalRecruiting
Seongnam-si, South Korea
Seoul National University HospitalRecruiting
Seoul, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
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 Aggressive B-Cell Non-Hodgkin's Lymphoma · TrialPath