Clinical trial NCT06806033: 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
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 Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-02-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of cytokine release syndrome (CRS)
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Incidence of serious cytokine release syndrome (CRS) events
timeFrame: Up to approximately 5 years
measure: CRS frequency relative to the start of glofitamab infusions
timeFrame: Up to approximately 5 years
measure: Complete response (CR) rate as determined by independent review facility (IRF) and the investigator
timeFrame: Up to approximately 5 years
measure: Overall response rate (ORR) as determined by IRF and the investigator
timeFrame: Up to approximately 5 years
measure: Duration of response (DOR)
timeFrame: 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)
measure: Duration of complete response (DOCR)
timeFrame: From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)
measure: Progression-free survival (PFS) as determined by the IRF and the investigator
timeFrame: From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (Up to approximately 5 years)
measure: Overall survival (OS)
timeFrame: From enrollment to date of death from any cause (Up to approximately 5 years)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology & Hematology, LLC
state: Alaska
city: Los Angeles
country: United States
facility: Valkyrie Clinical Trials
state: California
city: Boise
country: United States
facility: St Luke?s Cancer Institute
state: Idaho
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Center
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba (CCMB)
state: Manitoba
city: La Tronche
country: France
facility: CHU de Grenoble
city: Montpellier
country: France
facility: Chu de Montpellier-St Eloi
city: Pessac
country: France
facility: CHU de Bordeaux
city: Rennes
country: France
facility: CHU DE RENNES - CHU Pontchaillou
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Irccs Fondazione g. Pascale
state: Campania
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo studio dei tumori "Dino Amadori"
state: Emilia-Romagna
city: Brescia
country: Italy
facility: A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO)
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Hoffmann-La Roche
name: Study Director
role: STUDY_DIRECTOR
References: