Diffuse Large B-Cell Lymphoma (DLBCL)
Conditions
Keywords
Relapsed/Refractory, Glofitamab, Selinexor
Brief summary
Assess the efficacy and safety of glofitamab in combination with selinexor for the treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) in patients who have received at least two prior lines of systemic therapy.
Detailed description
Currently, patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) who have failed at least two lines of systemic therapy have a poor prognosis, and there is a significant clinical need for new treatment options. Glofitamab and selinexor have both demonstrated clinical activity as single agents in R/R DLBCL. Because their mechanisms of action are complementary and their toxicity profiles do not overlap significantly, this combination holds the potential to further improve outcomes. Therefore, this study plans to assess the efficacy and safety of glofitamab in combination with selinexor for the treatment of R/R DLBCL patients who have previously received at least two lines of systemic therapy. Enrolled patients will receive study treatments for up to 12 cycles, with each 21-day period being one cycle. Cycle 1 involves obinutuzumab pre-treatment and step-up dosing of glofitamab. From Cycle 2 to Cycle 12, patients will receive glofitamab in combination with oral selinexor. Interim efficacy evaluations will be conducted during the treatment. At the end of the 12 cycles or upon treatment discontinuation, a final efficacy evaluation will be conducted, followed by a long-term follow-up period.
Interventions
DRUGGlofitamab combined with selinexor
Patients receive obinutuzumab 1000 mg intravenously (IV) on Day 1 of Cycle 1 to mitigate cytokine release syndrome (CRS) risk. Glofitamab is administered IV with step-up dosing at 2.5 mg on Day 8 and 10 mg on Day 15 of Cycle 1, followed by a target dose of 30 mg on Day 1 of Cycles 2 through 12. Selinexor is administered orally at 60 mg on Days 1 and 3 of each week, starting from Cycle 2 through Cycle 12. Each cycle is 21 days. The total fixed duration of treatment is 12 cycles.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Zhejiang Provincial People's Hospital
The First Affiliated Hospital of Zhejiang Chinese Medical University
Zhejiang Provincial Tongde Hospital
Affiliated Hospital of Jiaxing University
Shaoxing People's Hospital
Shaoxing Central Hospital
Zhuji People's Hospital of Zhejiang Province
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years and older at the time of informed consent. * Histologically confirmed CD20+ diffuse large B-cell lymphoma (DLBCL). * Relapsed or refractory disease, having previously received at least two lines of systemic therapy. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. * Presence of measurable disease. * Adequate hematologic, hepatic, and renal function. * Willingness to use effective contraception methods during the study and for a specified period after the last dose. * Willing and able to provide written informed consent and comply with the study protocol.
Exclusion criteria
* Prior treatment with any CD20/CD3 bispecific antibodies or XPO1 inhibitors. * Current or prior history of central nervous system (CNS) involvement by lymphoma or other significant CNS diseases. * Active and uncontrolled systemic infections, including known HIV infection, active Hepatitis B virus (HBV), or active Hepatitis C virus (HCV) infection. * Active autoimmune diseases requiring systemic immunosuppressive therapy. * Clinically significant, severe, or uncontrolled cardiovascular diseases. * Other active invasive malignancies within the past 2 years (with exceptions for adequately treated localized cancers). * Recent major surgery or receipt of live attenuated vaccines within a specified timeframe prior to the study. * Severe gastrointestinal conditions that may significantly affect the absorption of oral medications. * Known severe allergic reactions to any of the study drugs or their excipients. * Pregnant or breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate (CRR) | Up to approximately 2 years | Proportion of patients achieving a best overall response of complete response (CR) as assessed by the investigator according to the 2014 Lugano Classification criteria based on PET/CT or CT scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 2 years | Proportion of patients achieving a best overall response of partial response (PR) or complete response (CR) as assessed by the investigator according to the 2014 Lugano Classification criteria. |
| Duration of Complete Response (DoCR) | Up to approximately 2 years | Time from the first documented complete response (CR) to the first documented disease progression or death from any cause, whichever occurs first. |
| Progression-Free Survival (PFS) | Up to approximately 2 years | Time from the start of study treatment to the first documented disease progression or death from any cause, whichever occurs first. |
| Overall Survival (OS) | Up to approximately 2 years | Time from the start of study treatment to death from any cause. |
| Incidence and Severity of Adverse Events (AEs) | From baseline up to 90 days after the last dose of study treatment (assessed up to approximately 2 years) | Incidence and severity of AEs graded according to NCI CTCAE v5.0, with Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) graded according to the ASTCT 2019 consensus criteria. |
Countries
China
Contacts
CONTACTJiefeng Tong
Outcome results
None listed