The goal of this clinical trial is to is to determine the safety, feasibility and efficacy of siltuximab prophylaxis of cytokine release syndrome and neurotoxicity occurring after epcoritamab subcutaneous administration for participants with large b-cell lymphoma (DLBCL) or follicular lymphoma (FL). Participants will receive siltuximab, prior to the injection of epcoritamab. Epcoritamab is administered in 28 day cycles for one year. After this injection, the physician will continue to watch participants for side effects and follow the condition for a minimum of 60 days.
Siltuximab is a monoclonal antibody that blocks interleukin-6 (IL-6) from binding to its receptor, preventing it from acting. IL-6 is a cytokine, a type of protein that is a cause of inflammatory reactions. Decreasing levels of IL-6 has been shown to reduce symptoms of cytokine release syndrome (CRS), a potential side effect of epcoritamab. Addition of siltuximab to the medications given before epcoritamab, may prevent, or reduce the severity, of CRS. Siltuximab is experimental because it is not approved by the Food and Drug Administration for treatment or prevention of CRS. Epcoritamab is a so-called bispecific antibody, which is a molecule that can bind simultaneously to two different receptors. Epcoritamab binds to a receptor called CD3 with one part of the antibody and to a receptor called CD20 with another part of the antibody. CD20 is expressed on the normal, healthy B cells but also on the cancerous lymphoma cells of B cell origin. CD3 is expressed on T cells, which are important cells of the immune system and help the body fight cancers, infections, etc. By simultaneous binding to CD3 and CD20, Epcoritamab brings T cells and B cells close together and activates the T cells to kill the B cells, including the cancerous ones.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Single dose of prophylactic siltuximab, 11mg/kg, started 1 hour prior (+/- 60 minutes) to the infusion of epcoritamab.
Epcoritamab dosing for Diffuse Large B-cell Lymphoma Participants: * Cycle 1, Day 1 = 0.16mg * Cycle 1, Day 8 = 0.8mg * Cycle 1, Day 15 = 48mg * Cycle 1, Day 22 = 48mg * Cycles 2 \& 3, Day 1 = 48mg * Cycles 2 \& 3, Day 8 = 48mg * Cycles 2 \& 3, Day 15 = 48mg * Cycles 2 \& 3, Day 22 = 48mg * Cycles 4-9, Day 1 = 48mg * Cycles 4-9, Day 15 = 48mg * Cycle 10+ , Day 1 = 48mg Epcoritamab dosing for Follicular Lymphoma Participants: * Cycle 1, Day 1 = 0.16mg * Cycle 1, Day 8 = 0.8mg * Cycle 1, Day 15 = 3mg * Cycle 1, Day 22 = 48mg * Cycle 2 \& 3, Day 1 = 48mg * Cycle 2 \& 3, Day 8 = 48mg * Cycle 2 \& 3, Day 15 = 48mg * Cycle 2 \& 3, Day 22 = 48mg * Cycle 4-9, Day 1 = 48mg * Cycle 4-9, Day 15 = 48mg * Cycle 10+ , Day 1 = 48mg
Starting on Cycle 2, participants may receive the addition of GemOx. Participants receive 1,000 milligrams/meter\^2 (mg/m\^2) of GemOx on Days 1 and 15 of Cycle 2 and onwards.
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
RECRUITINGIncidence of all-grade cytokine release syndrome
The primary objective is to evaluate the feasibility and efficacy of prophylactic administration of siltuximab prior to infusion of the first dose of epcoritamab with the purpose of preventing all-grade CRS, as measured by incidence of all-grade cytokine release syndrome.
Time frame: Up to 28 days after beginning treatment
Incidence of grade ≥ 2 cytokine release syndrome
A secondary objective is to determine the incidence of grade ≥ 2 CRS after siltuximab prophylaxis
Time frame: Up to 28 days after beginning treatment
Incidence of all grade and grade ≥ 2 ICANS after siltuximab prophylaxis
A secondary objective is to determine the incidence of all grade and grade ≥ 2 ICANS after siltuximab prophylaxis
Time frame: Up to 28 days beginning treatment
Incidence of adverse events during Cycle 1 (Day 1 - 28)
A secondary objective is to describe the adverse events after siltuximab prophylaxis.
Time frame: Up to 28 days after beginning treatment
Best overall and complete response rates
A secondary objective is to describe the disease response rates (overall and complete response rates) to epcoritamab in participants treated with prophylactic siltuximab, based on Lugano response criteria for malignant lymphomas, which can include complete response (CR), partial response (PR), stable disease (SD), progression (PD) and relapse.
Time frame: Up to 456 days after beginning treatment
Incidence of hospitalizations secondary to all causes
A secondary objective is to describe the rates of hospitalization for all causes and for cytokine release syndrome
Time frame: Up to 456 days after beginning treatment
Incidence of hospitalizations secondary to cytokine release syndrome or neurologic complications
A secondary objective is to describe the rates of hospitalization for for cytokine release syndrome
Time frame: Up to 456 days after beginning treatment
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