Not yet recruitingRare disease

Phase II study of fixed‑dose, accelerated ramp‑up epcoritamab plus lenalidomide in patients with relapsed/refractory large B‑cell lymphoma after CAR‑T therapy

Verified siteRegistered drugNo placebo

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on people who have large B-cell lymphoma that has come back or did not respond after a previous CAR T-cells therapy given in the second line of treatment. The investigation tests a fixed dose and a faster increase schedule of epcoritamab, which is given as a subcutaneous injection (an injection placed under the skin), together with lenalidomide, which is taken oral (by mouth). “Relapse/refractory” means the cancer has returned or does not improve with standard therapy, and “CAR T-cells therapy” is a special treatment that uses a patient’s own immune cells that have been changed to attack the cancer.

The purpose of the trial is to determine how well this combination can shrink or control the disease. Participants receive the injection of epcoritamab and the pill of lenalidomide over several treatment cycles, with regular visits to check health, monitor the cancer’s response, and watch for any side effects. After the treatment period, patients continue to be followed to see how long any benefit lasts and to ensure safety.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Start treatment
The first day after joining the study you will receive a subcutaneous injection of epcoritamab at a dose of 48 mg.
You will also begin taking oral tablets of lenalidomide at a dose of 20 mg, according to the schedule set by the study protocol.
Step 2
Continue epcoritamab injections
Subsequent epcoritamab injections are given at the fixed dose of 48 mg following an accelerated ramp‑up schedule defined by the study.
The injections are administered under medical supervision at the intervals specified in the protocol.
Step 3
Continue lenalidomide tablets
You will keep taking lenalidomide tablets at 20 mg each day for the duration of the treatment period, unless the study team advises a change.
Step 4
Response assessments
The study team will evaluate how the disease is responding after each treatment cycle.
Assessments are performed after cycle 1 (c1), cycle 2 (c2), cycle 5 (c5), cycle 8 (c8), and at the end of treatment.
These evaluations use imaging and clinical criteria to determine whether the disease has improved.
Step 5
Treatment continuation
Treatment continues until one of the following occurs: disease progression, relapse, unacceptable side effects, or the planned end of the treatment period.
The overall response is recorded after cycle 2 or at the end of treatment, whichever happens first.
Step 6
Post‑treatment follow‑up
After stopping the study medication, you will attend follow‑up visits to monitor for any late effects and to record overall survival and safety outcomes.

Who can join the trial?

23 criteria

You (or a trusted person acting for you) must understand the study and voluntarily sign and date an informed consent form before any study procedures begin.
Your liver must be working well enough: the total bilirubin level must be no more than 1.5 times the normal upper limit, and the enzymes called AST and ALT must be no more than 3 times the normal upper limit. If you have Gilbert’s syndrome (a harmless condition that can raise bilirubin), you are still eligible as long as the bilirubin increase is mainly the indirect type.
You must not have ongoing nerve or brain side‑effects from the previous CAR‑T cell therapy, no matter how mild or severe.
Any side‑effects from earlier cancer treatments must have improved to a mild level (grade 1 or lower), except for a few specific conditions listed in the protocol.
You need a negative HIV test, unless you are HIV‑positive and have been stable on antiretroviral medication for at least 4 weeks, have a CD4 cell count of 200 cells/µL or higher, have an undetectable viral load, and have not had a serious AIDS‑related infection in the past year.
You must not be resistant (“refractory”) to drugs called IMiDs (immunomodulatory drugs) and must be judged suitable for treatment with lenalidomide. Refractory means your best response to a prior IMiD was only stable disease or progression, or the disease got worse within 6 months after finishing the IMiD.
You must not have taken lenalidomide in the 12 months before screening.
You must be willing to take aspirin or another blood‑clot‑preventing medicine as recommended for patients receiving lenalidomide.
You must be able to swallow capsules and should not have major stomach or intestine problems such as removal of the stomach or small bowel, active inflammatory bowel disease, or a blockage in the bowel.
If you are a woman who could become pregnant, you must have a negative pregnancy test, use an effective birth‑control method from 4 weeks before starting treatment until 4 weeks after the last dose of lenalidomide and 4 months after the last dose of epcoritamab, agree not to breast‑feed during the study and for at least 4 months after the last dose, and agree not to donate eggs during the study and until the same time periods after treatment.
If you are a man who could father a child, you must use an acceptable birth‑control method (such as condoms) and agree not to donate sperm during treatment and for 7 days after the last dose of lenalidomide and 4 months after the last dose of epcoritamab.
You must be at least 18 years old when you sign the consent form; there is no upper age limit.
You must agree to follow the pregnancy‑risk‑reduction plan that comes with lenalidomide treatment.
You must be covered by a social‑security system in France.
You need to have a life expectancy of at least 3 months.
You must understand and be able to speak one of the official languages of the country (or have a permitted translator).
You must have a confirmed diagnosis of relapse or progression of large B‑cell lymphoma (including several subtypes listed) after CAR‑T cell therapy, with the cancer cells showing the marker CD20. Certain other lymphoma types (such as chronic lymphocytic leukemia, indolent non‑Hodgkin lymphoma, transformed Waldenström macroglobulinemia, transformed marginal‑zone lymphoma, and Burkitt lymphoma) are excluded.
You must not have received epcoritamab or any other bispecific antibody that targets both CD3 and CD20 before.
You must have disease that has come back or not responded after two separate lines of systemic therapy, one of which must include CAR‑T cell therapy given as second‑line treatment (bridging therapy does not count as a line). Relapse or refractory status must be shown by a PET scan about 1 month after the CAR‑T infusion or on later scans. If you received CAR‑T cells together with an IMiD as second‑line therapy, you are not eligible.
Your overall health performance, measured by the ECOG scale, must be 0, 1, or 2 (0 = fully active, 2 = able to walk and take care of yourself but not fully active).
You must have disease that can be measured: at least one lymph node larger than 15 mm or an outside‑lymph‑node lesion larger than 10 mm, and at least one area that lights up on a PET‑CT scan (a special imaging test that shows active cancer).
Your blood‑forming (hematopoietic) system must be adequate: hemoglobin level higher than 8 g/dL (without a red‑blood‑cell transfusion in the past week), absolute neutrophil count (a type of white blood cell) at least 1 × 10⁹/L (or at least 0.5 × 10⁹/L if low because the lymphoma is in the bone marrow), and platelet count at least 50 × 10⁹/L (or at least 30 × 10⁹/L if low because of lymphoma or an enlarged spleen), without a platelet transfusion in the past week.
Your kidneys must work well enough: calculated creatinine clearance must be at least 40 mL/min, using either the MDRD or Cockcroft‑Gault formula.

Who cannot join the trial?

27 criteria

You cannot join if tests show your cancer cells do not have the protein CD20, unless a new biopsy proves CD20 is present.
You cannot join if you have an active infection or a re‑activated hidden infection (bacterial, viral such as COVID‑19, fungal, mycobacterial, or other), or if you were hospitalized or needed IV antibiotics for an infection within one week before the first study drug dose.
You cannot join if blood tests show you have a positive result for HTLV‑1 (a type of virus).
You cannot join if you have an active Hepatitis C infection (detectable viral RNA). If you have been treated and the virus is no longer detectable, you may be allowed.
You cannot join if you have an active Hepatitis B infection (detectable viral DNA).
You cannot join if your heart’s pumping ability, measured as left ventricular ejection fraction (LVEF), is less than 45% on an ultrasound (echocardiogram) or a special scan (MUGA).
You cannot join if you have a serious heart condition such as advanced heart failure (NYHA class III or IV), severe irregular heartbeat, a heart attack in the past six months, unstable chest pain, or serious lung disease (including uncontrolled asthma‑like disease or frequent bronchospasm).
You cannot join if you have uncontrolled liver scarring (cirrhosis).
You cannot join if you had major surgery or a serious injury within the past 28 days, or if you are expected to need major surgery while taking the study drug.
You cannot join if you have taken strong immune‑suppressing medicines (such as cyclophosphamide, azathioprine, methotrexate, thalidomide, or anti‑TNF drugs) within two weeks before the first dose, except low‑dose steroids (less than 25 mg prednisone daily). Inhaled or skin‑applied steroids are allowed.
You cannot join if you have another active cancer besides the lymphoma being studied.
You cannot join if you have ever received a solid organ transplant (for example, kidney or liver).
You cannot join if you had a different cancer in the past unless you have been disease‑free for at least two years, with some exceptions for very early skin or breast cancers, small prostate cancers, or certain cervical cancers.
You cannot join if you are known or think you might be allergic to the study drug or any of its inactive ingredients.
You cannot join if, within the last four weeks (or five drug half‑lives, whichever is shorter), you received radiation therapy, chemotherapy, other experimental cancer drugs, or systemic immune therapies (such as radio‑immunoconjugates, antibody‑drug conjugates, cytokines, or monoclonal antibodies like anti‑CTLA‑4, anti‑PD‑1, anti‑PD‑L1).
You cannot join if you are pregnant, planning to become pregnant, breastfeeding, or of child‑bearing potential without effective birth control.
You cannot join if you have any other serious medical problem, abnormal lab test, or mental health condition that the doctor thinks would make participation unsafe or difficult.
You cannot join if a court or government authority has taken away your personal freedom.
You cannot join if you are currently hospitalized without your consent.
You cannot join if a legal guardian has been appointed to make decisions for you.
You cannot join if you have had an allogeneic stem cell transplant (donor cells).
You cannot join if you received an autologous stem cell transplant (your own cells) within the past 100 days.
You cannot join if your lymphoma has spread to the brain or the lining of the brain (meninges).
You cannot join if you have ever had Progressive Multifocal Leukoencephalopathy (PML), a rare brain infection.
You cannot join if you have a history of serious brain or nerve problems such as aphasia, delirium, dementia, cerebellar disease, cognitive disorders, treated epilepsy, brain‑blood‑vessel inflammation, neurodegenerative disease, or speech difficulties.
You cannot join if you have had a stroke or brain bleed that left lasting effects.
You cannot join if you have a serious psychiatric illness that would prevent you from signing the consent form.

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

CHRU De Nancy
Responsive
Vandoeuvre Les Nancy, France
Centre Hospitalier Et Universitaire De Limoges
Verified
Limoges, France
Centre Hospitalier Lyon Sud
Verified
Pierre Benite, France

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Investigated drugs

Epcoritamab (GEN3013)
is a laboratory‑made antibody that is given as a subcutaneous injection. In this study it is being tested as a fixed dose that is started quickly (accelerated ramp‑up). The drug is designed to help the immune system recognize and attack large B‑cell lymphoma cells that have come back after earlier CAR‑T cell therapy.
Lenalidomide
is an oral medication taken by mouth. It works by modifying the activity of immune cells and by directly slowing the growth of certain cancer cells. In this trial it is combined with epcoritamab to see if the two together improve outcomes for patients whose lymphoma has returned after previous treatments.

What is already known about the treatment

Epcoritamab
Epcoritamab is given as a subcutaneous injection of a clear solution, with a fixed dose of 48 mg. It is still an investigational drug being studied in clinical trials for patients whose large B‑cell lymphoma has returned after CAR‑T cell therapy. The medicine works by attaching to both T‑cells and cancer B‑cells, helping the immune system recognize and destroy the tumor cells. It belongs to the class of bispecific antibodies that engage T‑cells to target cancer.
Lenalidomide
Lenalidomide is taken orally as a tablet, usually at a dose of 20 mg per day. It is an approved medication for several blood cancers and is now being tested together with epcoritamab for relapsed large B‑cell lymphoma. The drug helps the immune system work better and blocks signals that let cancer cells grow and form new blood vessels. It is classified as an immunomodulatory drug.

Investigated diseases

Relapsed/refractory large B-cell lymphoma - Large B-cell lymphoma is a fast‑growing blood cancer that starts in large B lymphocytes, often causing swollen lymph nodes and sometimes affecting the spleen, bone marrow, or other organs. When the disease returns or does not respond after initial treatment, it is called relapsed or refractory. In this state the cancer can continue to enlarge existing tumors and appear in new locations. The disease may spread to the blood, bone marrow, or other organs, leading to worsening symptoms such as fever, weight loss, and night sweats. Without effective control, the tumor burden can increase steadily over time.