Study of Cytokine Release Syndrome Prophylaxis and Treatment With Siltuximab Prior to Epcoritamab

NCT06447376 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE1424
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Hodgkin Lymphoma; Cytokine Release Syndrome

Keywords

Siltuximab; Epcoritamab; Prophylactic siltuximab

Outcome Measures

Primary Outcomes (1)

• Incidence 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.

  Up to 28 days after beginning treatment

Secondary Outcomes (6)

• Incidence of grade ≥ 2 cytokine release syndrome

  Up to 28 days after beginning treatment

• Incidence of all grade and grade ≥ 2 ICANS after siltuximab prophylaxis

  Up to 28 days beginning treatment

• Incidence of adverse events during Cycle 1 (Day 1 - 28)

  Up to 28 days after beginning treatment

• Best overall and complete response rates

  Up to 456 days after beginning treatment

• Incidence of hospitalizations secondary to all causes

  Up to 456 days after beginning treatment

Study Arms (1)

Prophylactic siltuximab + epcoritamab

EXPERIMENTAL

Siltuximab Administration: • Participants will receive a single dose of prophylactic siltuximab, 11mg/kg, started 1 hour prior (+/- 60 minutes) to the infusion of epcoritamab. There is no planned dose escalation of siltuximab and epcoritamab dosing will be done following the standard planned ramp-up over the course of the first 3 weeks Epcoritamab Infusion: • The treatment regimen of epcoritamab is done in 28-day cycles. Epcoritamab is to be administered by subcutaneous injection. Participants can be treated for up to 24 cycles. Participants who achieve complete remission at the time of their disease response assessment after 12 cycles may be considered for early discontinuation of treatment.

Drug: Siltuximab; Drug: Epcoritamab

Interventions

Siltuximab DRUG

Single dose of prophylactic siltuximab, 11mg/kg, started 1 hour prior (+/- 60 minutes) to the infusion of epcoritamab.

Prophylactic siltuximab + epcoritamab

Epcoritamab DRUG

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

Prophylactic siltuximab + epcoritamab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18 years of age and older
• Diagnosis of non-Hodgkin lymphoma.
• DLBCL (including high grade B cell lymphoma and follicular lymphoma grade 3B and transformed follicular lymphoma) treated with at least 2 lines of systemic antineoplastic therapies, including at least 1 anti-CD20 monoclonal antibody - containing therapy
• FL grade 1-3A previously treated with at least 2 lines of systemic antineoplastic therapy, including at least 1 anti-CD20 monoclonal antibody - containing therapy.
• At least 1 risk factor for cytokine release syndrome, including:
• Age ≥ 65 years,
• Elevated lactate dehydrogenase,
• White blood cell count pre-anti-CD20 treatment \> 4.5x109 cells/L,
• Ann Arbor Stage III/IV,
• Sum of the product of the perpendicular diameters at study entry ≥3000mm2,
• Cardiac comorbidity, including prior coronary disease, heart failure and other conditions that in the opinion of the investigator would increase the risk of heightened toxicity from CRS
• Bone marrow infiltration,
• Circulating lymphoma cells in peripheral blood
• Adequate bone marrow function including:
• Hemoglobin ≥ 8g/dL (unless bone marrow involvement by lymphoma) (transfusion allowed for symptomatic participants),

You may not qualify if:

• Primary mediastinal B cell lymphoma
• Active central nervous system or meningeal involvement by lymphoma
• History of severe allergic or anaphylactic reactions to anti-CD20 monoclonal antibody therapy
• Active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic therapy within 2 weeks prior to first dose of study drug. This includes participants with COVID-19 infection
• Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast). History of prior malignancy is not excluded.
• HIV seropositivity.
• Subjects with uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because siltuximab therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with siltuximab, breastfeeding should be continued and not restarted for 3 months after the last dose of siltuximab. These potential risks may also apply to other agents used in this study.
• Participants with history of clinically relevant and active CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.

Sponsors & Collaborators

• Taylor Brooks: lead
• Genmab: collaborator
• AbbVie: collaborator
• RECORDATI GROUP: collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Cytokine Release Syndrome

Interventions

siltuximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Taylor Brooks, MD

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Taylor Brooks, MD

CONTACT

1-866-223 8100; TaussigResearch@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: IND Holder

Model Details: Single cohort study.

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: January 14, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available during the course of the trial and indefinitely thereafter.
• Access Criteria: Data will be available for the FDA otherwise a confidentiality agreement will need to be in place

Locations

US (1)