Epcoritamab and Lenalidomide in Treating Patients With Refractory or Relapsed Immunodeficiency-Related Large B-Cell Lymphoma

Recruiting now · Phase 2

Conditions studied: Recurrent B-Cell Non-Hodgkin Lymphoma, Recurrent Polymorphic Post-Transplant Lymphoproliferative Disorder, Refractory B-Cell Non-Hodgkin Lymphoma

In brief

This phase II trial tests how well the combination of epcoritamab and lenalidomide work in treating patients with immunodeficiency-related large B-cell lymphoma that does not respond to treatment (refractory) or that has come back after a period of improvement (relapsed). Epcoritamab is an immunotherapy that engages T-cells in the immune system to help redirect their killing effects against lymphoma cells. Lenalidomide can modulate the immune system to enhance killing effects of lymphoma by the immune system as well. Giving patients a combination of epcoritamab and lenalidomide may work better in treating refractory or relapsed immunodeficiency-related large B-cell lymphoma.

Key facts

Study ID

NCT06723457

Run by

Reem Karmali

People needed

34

Starts

2025-07-25

Expected to finish

2029-02-18

Last updated by the study team

2026-07-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have a pathologically confirmed diagnosis of immunodeficiency-related large B-cell lymphoma as defined by the 5th Edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors 2022 in addition to any of the following:
• Lymphomas arising in immune deficiency which encompass monomorphic post-transplant lymphoproliferative disorder (PTLD) OR
• Polymorphic B-cell lymphoproliferative disorder arising in the setting of immunodeficiency and/or immune dysregulation as seen in 1 or more of the following settings:
• Underlying autoimmune disease
• Iatrogenic or therapy-related immunosuppression
• Conditions arising from inborn errors of immunity
• Immune senescence as seen in patients aged ≥80 years or those ≥ 65 years with CD4 count < 500 cells/mm\^3
• Epstein-Barr virus (EBV) infection as demonstrated by EBV positivity in the tumor cells
• Patients must have measurable disease (≥ 1 measurable nodal lesion [long axis > 1.5 cm] or ≥ 1 measurable extra-nodal lesion [long axis > 1.0 cm] on CT scan or MRI) per Lugano criteria
• Note; Patients with hepatomegaly /organomegaly deemed to be related to disease will also be eligible if not meeting strict Lugano criteria
• Patients must meet one disease status as follows AND deemed ineligible for chimeric antigen receptor T-cell (CAR-T):
• Primary refractoriness defined as a partial response or less on interim PET-CT during therapy with frontline chemo-immunotherapy (containing anti-CD20 monoclonal antibody)
• Primary refractoriness defined as a partial response or less on interim PET-CT during therapy with rituximab (or any other anti-CD20 monoclonal antibody) monotherapy AND deemed ineligible for escalation to chemotherapy
• Relapse after achieving a complete response with ≥ 1 prior systemic therapy (including CART)
• Patients must be aged ≥ 18 years
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count (ANC) ≥ 1000/mcL (the use of growth factor support to attain goal ANC allowed, but not the last 14 days prior to screening laboratory test)
• Platelets (PLT) ≥ 50,000/mcL (transfusions allowed ≥ 7 days prior)
• Total bilirubin ≤ 1.5 Institutional upper limit of normal (ULN) unless attributed to Gilbert's ≤ 3 Institutional ULN if attributed to disease or Gilbert's
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 x institutional ULN (> 3 and ≤ 5 x institutional upper limit of normal (ULN) if deemed related to disease)
• Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2
• Estimated (e)GFR is calculated by the abbreviated Modification of Diet in Renal Disease (MDRD)
• For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

You may not qualify if…

• Patients who have received any prior therapy with a bispecific T-cell engager targeting CD3 and CD20
• Patients who have received chemotherapy and/or other antineoplastic agents (except CD20- targeting monoclonal antibodies, steroids and/or radiation) within 1 week or 5 half-lives (whichever is shorter) prior to registration
• Patients who have undergone autologous stem cell transplant (ASCT) within 100 days of registration
• Patients who have undergone CAR-T therapy with refractoriness or relapse within 30 days of registration
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab and/or lenalidomide
• Patients with human immunodeficiency virus (HIV) with detectable viral load and CD4 count ≤350 cells/mm3 \& not on treatment for more than 1 year
• Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI or cerebrospinal fluid (CSF) studies obtained within 4 weeks prior to registration or progressive neurological decline, attributable to CNS disease
• Patients who have a seizure disorder that is not controlled (requiring anti-epileptic therapy AND with seizure within 12 months of registration)
• Patients who have had major surgery within 4 weeks prior to registration
• Patients who have clinically significant cardiac disease include the following:
• Myocardial infarction or stroke within 6 months prior to enrollment,
• OR the following conditions within 6 months prior to enrollment: unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV), uncontrolled cardiac arrhythmia, and uncontrolled hypertension),
• OR Other clinically significant electrocardiogram (ECG) abnormalities within 6 months prior to enrollment unless deemed stable and appropriately treated
• OR Left ventricular ejection fraction < 45% for Echocardiogram
• Patients who are unable to swallow, retain and absorb oral tablet/gel/capsules
• Patients who have received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention.
• Note: Administration of killed vaccines is allowed
• Female patients who are pregnant or nursing.
• Note: Females should refrain from breast feeding from the time of informed consent, during the study and for 12 months after the last dose of study treatment
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Ongoing or active infection requiring IV antimicrobial treatment
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints

Where it is running

• Northwestern University — Chicago, Illinois, United States (enrolling)

Full record on ClinicalTrials.gov

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