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NCT06806033PHASE2Recruiting

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

Hoffmann-La Roche

Start Date

3/5/2025

Completion Date

3/30/2029

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 Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Obinutuzumab

DRUG

Glofitamab

DRUG

Gemcitabine

DRUG

Oxaliplatin

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Conditions

B-Cell Non-Hodgkins Lymphoma

Locations

Alaska Oncology & Hematology, LLC

Anchorage, Alaska 99508

United States

Community Cancer Institute (CCI)

Clovis, California 93611

United States

Providence Medical Foundation

Fullerton, California 92835

United States

Los Angeles Cancer Network

Glendale, California 91204

United States

Valkyrie Clinical Trials

Los Angeles, California 90067

United States

Valkyrie Clinical Trials

Panorama City, California 91402

United States

Zuckerberg San Francisco General Hospital

San Francisco, California 94110

United States

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

Torrance, California 90502-2006

United States

Rocky Mountain Cancer Centers, LLP

Aurora, Colorado 80012

United States

North Florida/ South Georgia VA Medical Center

Gainesville, Florida 32608

United States

Mount Sinai Comprehensive Cancer Center

Miami, Florida 33140

United States

Orlando Health Cancer Institute

Orlando, Florida 32806

United States

St Luke?s Cancer Institute

Boise, Idaho 83712

United States

Cancer Care Specialists of Central Illinois

Swansea, Illinois 62226

United States

Mission Blood and Cancer - MercyOne Cancer Center

Waukee, Iowa 50263

United States

University of Kentucky - Markey Cancer Center

Lexington, Kentucky 40536

United States

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana 70809

United States

Boston Medical Center

Boston, Massachusetts 02118

United States

Corewell Health

Grand Rapids, Michigan 49503

United States

Nebraska Cancer Specialists

Omaha, Nebraska 68130

United States

New York Oncology Hematology, P.C.

Albany, New York 12206

United States

Hematology Oncology Associates of Central New York

East Syracuse, New York 13057

United States

Oncology Associates of Oregon, P.C

Eugene, Oregon 97401

United States

Providence Portland Medical Center

Portland, Oregon 97213

United States

Providence St. Vincent Medical Center

Portland, Oregon 97225

United States

Tennessee Oncology

Chattanooga, Tennessee 37403

United States

Tennessee Oncology

Nashville, Tennessee 37203

United States

Baylor Scott & White Health

Temple, Texas 76502

United States

Texas Oncology - Gulf Coast

The Woodlands, Texas 77380

United States

Texas Oncology- Northeast Texas

Tyler, Texas 75702

United States

Virginia Cancer Specialists, PC

Fairfax, Virginia 22031

United States

Virginia Oncology Associates - Virginia Beach

Virginia Beach, Virginia 23456

United States

Northwest Medical Specialties

Tacoma, Washington 98405

United States

Epworth Hospital

East Melbourne, Victoria 3002

Australia

Arthur J.E. Child Comprehensive Cancer Center

Calgary, Alberta T2N 5G2

Canada

CancerCare Manitoba (CCMB)

Winnipeg, Manitoba R3E 0V9

Canada

CHU de Grenoble

La Tronche, 38700

France

Chu de Montpellier-St Eloi

Montpellier, 34295

France

CHU de Bordeaux

Pessac, 33600

France

CHU DE RENNES - CHU Pontchaillou

Rennes, 35033

France

Chu De Tours

Tours, 37000

France

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

Berlin, 12200

Germany

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

Berlin, 13353

Germany

Universitätsklinikum Köln

Cologne, 50937

Germany

Otto von Guericke Uni Magdeburg Uniklinik

Magdeburg, 39120

Germany

Istituto Nazionale Tumori Irccs Fondazione g. Pascale

Naples, Campania 80131

Italy

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

Meldola, Emilia-Romagna 47014

Italy

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

Brescia, Lombardy 25123

Italy

Irccs Istituto Europeo Di Oncologia (IEO)

Milan, Lombardy 20141

Italy

Istituto Clinico Humanitas

Rozzano, Lombardy 20089

Italy

Seoul National University Bundang Hospital

Seongnam-si, 463-707

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea