Clinical trial NCT06624085: A Study Evaluating the Safety and Efficacy of Glofitamab + Gemcitabine + Oxaliplatin in U.S. Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Official title: A Phase Ib Study Evaluating the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in U.S. Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2024-10-02
Enrollment: 50
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 purpose of the study is to evaluate glofitamab + gemcitabine + oxaliplatin in participants in the United States, including under-represented racial and ethnic populations, that have relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed DLBCL, not otherwise specified (NOS)
* Relapsed (disease that has recurred following a response that lasted ≥ 6 months after completion of the last line of therapy) or refractory ( disease that did not respond to or that progressed \< 6 months after completion of the last line of therapy) disease
* At least one prior line of 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) Performance Status of 0, 1, or 2

Exclusion Criteria:

* Prior enrollment in Study GO41944 (STARGLO; NCT04408638)
* 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
* 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 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 CNS lymphoma
* Prior CNS involvement that has been definitively treated and confirmed via 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, or significant pulmonary disease
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (exclusing fungal infections of nail beds) at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment
* Documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 6 months of first study treatment, or positive SARS-CoV-2 test within 7 days prior to enrollment
* Suspected or latent tuberculosis
* Positive test results for hepatitis B (HBV) or hepatitis C (HCV)
* Known or suspected chronic active Epstein-Barr viral infection
* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
* Known history of progressive multifocal leukoencephalopathy
* Prior solid organ transplantation
* Prior allogenic stem cell transplant
* Active autoimmune disease requiring treatment
* Prior treatment with systemic immunosuppressive medications within 4 weeks prior to first dose of study treatment
* Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the patient 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 3 years
measure: Complete response (CR) rate
timeFrame: Up to 3 years
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 3 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 3 years)
measure: Duration of CR
timeFrame: From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to 3 years)
measure: Progression-free survival (PFS)
timeFrame: From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 3 years)
measure: Overall Survival (OS)
timeFrame: From enrollment to date of death from any cause (up to 3 years)
measure: Serum concentration of glofitamab
timeFrame: Up to 3 years
measure: Incidence of anti-drug antibodies to glofitamab
timeFrame: Baseline up to 3 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Laguna Hills
country: United States
facility: Saddleback Memorial Medical Center
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: El Paso
country: United States
facility: Renovatio Clinical - El Paso
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: