RecruitingPhase 2NCT06806033

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

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


Sponsor

Hoffmann-La Roche

Enrollment

100 participants

Start Date

Mar 5, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria8

  • 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 Criteria30

  • 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

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).


Locations(51)

Alaska Oncology & Hematology, LLC

Anchorage, Alaska, United States

Community Cancer Institute (CCI)

Clovis, California, United States

Providence Medical Foundation

Fullerton, California, United States

Los Angeles Cancer Network

Glendale, California, United States

Valkyrie Clinical Trials

Los Angeles, California, United States

Zuckerberg San Francisco General Hospital

San Francisco, California, United States

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

Torrance, California, United States

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado, United States

North Florida/ South Georgia VA Medical Center

Gainesville, Florida, United States

Mount Sinai Comprehensive Cancer Center

Miami, Florida, United States

Orlando Health Cancer Institute

Orlando, Florida, United States

St Luke?s Cancer Institute

Boise, Idaho, United States

Cancer Care Specialists of Central Illinois

Swansea, Illinois, United States

Mission Blood and Cancer - MercyOne Cancer Center

Waukee, Iowa, United States

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, United States

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana, United States

Boston Medical Center

Boston, Massachusetts, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

Hematology Oncology Associates of Central New York

East Syracuse, New York, United States

Oncology Associates of Oregon, P.C

Eugene, Oregon, United States

Providence Portland Medical Center

Portland, Oregon, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

Tennessee Oncology

Chattanooga, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

Baylor Scott & White Health

Temple, Texas, United States

Texas Oncology - Gulf Coast

The Woodlands, Texas, United States

Texas Oncology- Northeast Texas

Tyler, Texas, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Virginia Oncology Associates - Virginia Beach

Virginia Beach, Virginia, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Epworth Hospital

East Melbourne, Victoria, Australia

Arthur J.E. Child Comprehensive Cancer Center

Calgary, Alberta, Canada

CancerCare Manitoba (CCMB)

Winnipeg, Manitoba, Canada

CHU de Grenoble

La Tronche, France

Chu de Montpellier-St Eloi

Montpellier, France

CHU de Bordeaux

Pessac, France

CHU DE RENNES - CHU Pontchaillou

Rennes, France

Chu De Tours

Tours, France

CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie

Berlin, Germany

Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK)

Berlin, Germany

Universitätsklinikum Köln

Cologne, Germany

Otto von Guericke Uni Magdeburg Uniklinik

Magdeburg, Germany

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Napoli, Campania, Italy

IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"

Meldola, Emilia-Romagna, Italy

A.O. Spedali Civili Di Brescia-P.O. Spedali Civili

Brescia, Lombardy, Italy

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy, Italy

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Seoul National University Hospital

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

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NCT06806033