Epcoritamab + Lenalidomide for B-Cell Lymphoma

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Bispecific T-cell engagers

Disqualifiers: HIV, CNS disease, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 32

Duration: 12 months

34 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received chemotherapy or other antineoplastic agents (except certain antibodies, steroids, or radiation) within 1 week or 5 half-lives before joining the trial.

What data supports the effectiveness of the drug combination Epcoritamab and Lenalidomide for B-Cell Lymphoma?

Research shows that Lenalidomide, when used with other drugs like rituximab, has been effective in treating various types of B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma. It works by boosting the immune system to fight cancer cells and has shown promising results in improving patient outcomes. ^{1 2 3 4 5}

Is the combination of Epcoritamab and Lenalidomide safe for treating B-cell lymphoma?

Lenalidomide, also known as Revlimid, has been shown to have a generally favorable safety profile in treating B-cell lymphomas, though it can cause some serious side effects like neutropenia (low white blood cell count) and febrile neutropenia (fever with low white blood cell count). These side effects are often manageable with dose adjustments and additional treatments. ^{1 3 4 6 7}

How is the drug combination of Epcoritamab and Lenalidomide unique for treating B-cell lymphoma?

The combination of Epcoritamab and Lenalidomide is unique because it pairs an immunomodulatory drug (Lenalidomide) with a novel agent (Epcoritamab) that may enhance immune response against B-cell lymphoma, offering a potentially new approach compared to traditional chemotherapy. ^{1 3 5 8 9}

What is the purpose of this trial?

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.

Research Team

Reem Karmali

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for patients with immunodeficiency-related large B-cell lymphoma that has either not responded to previous treatments or has returned after treatment. Participants should have a type of non-Hodgkin's lymphoma and be in a relapsed or refractory state.

Inclusion Criteria

I have chronic hepatitis B but it's under control with treatment.

I agree to use birth control if I can become pregnant.

Patients must have measurable disease per Lugano criteria

Exclusion Criteria

My cancer did not respond or came back within 30 days after CAR-T therapy.

Patients with human immunodeficiency virus (HIV) with detectable viral load and CD4 count ≤350 cells/mm3 & not on treatment for more than 1 year

I have active cancer in my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive epcoritamab subcutaneously and lenalidomide orally in cycles repeating every 28 days for up to 12 months

12 months

Weekly visits during cycle 1, then multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at 30 days, 12, 18, and 24 months

Treatment Details

Interventions

• Epcoritamab
• Lenalidomide

Trial Overview The trial is testing the effectiveness of combining two drugs, Epcoritamab and Lenalidomide, on treating this specific lymphoma. Epcoritamab helps direct the immune system's T-cells to attack cancer cells, while Lenalidomide boosts the immune response against these cells.

Participant Groups

Group I: Treatment (epcoritamab, lenalidomide) Experimental Treatment 6 Interventions

Patients receive epcoritamab SC weekly during cycle 1 and on days 1, 8, 15, and 22 of cycles 2-3, and day 1 of cycles 4-12. Patients also receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and collection of blood samples throughout the study and may undergo MRI during screening.

Epcoritamab is already approved in United States, European Union for the following indications:

Approved in United States as Epkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Diffuse large B-cell lymphoma after two or more lines of systemic therapy

Approved in European Union as Tepkinly for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
• Relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide is an FDA-approved immunomodulatory drug that shows strong efficacy in treating multiple myeloma and certain B-cell malignancies, particularly when combined with monoclonal antibodies like rituximab.

The drug works by modifying the tumor microenvironment and enhancing the activity of T and natural-killer (NK) cells, demonstrating excellent tolerability and potential to change treatment approaches for non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Arora, M., Gowda, S., Tuscano, J.[2022]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

In a phase II trial involving 66 patients with untreated follicular lymphoma, the combination of lenalidomide and rituximab achieved a high overall response rate of 95% and a complete response rate of 72%, indicating strong efficacy.

The treatment was associated with low rates of severe toxicity (grade 3-4), with a 5-year overall survival rate of 100%, suggesting that lenalidomide plus rituximab could be a safe and effective alternative to traditional chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Martin, P., Jung, SH., Pitcher, B., et al.[2023]

Lenalidomide, an immunomodulatory drug, shows promise in treating diffuse large B-cell lymphoma (DLBCL) due to its multiple mechanisms of action that may enhance the effectiveness of existing immunochemotherapy treatments.

Current survival rates for DLBCL indicate a need for new treatment options, and lenalidomide has demonstrated potential benefits in both relapsed/refractory cases and as a first-line treatment based on recent clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in diffuse large B-cell lymphoma. Thieblemont, C., Delfau-Larue, MH., Coiffier, B.[2021]

Lenalidomide significantly improves the complete response rate (CRR) in patients with diffuse large B-cell lymphoma (DLBCL), achieving a CRR of 47.7% compared to 37.8% in the control group, based on a meta-analysis of 6 randomized controlled trials involving 1938 patients.

While lenalidomide enhances progression-free survival (PFS), it is associated with a higher risk of severe hematological adverse events, particularly neutropenia and febrile neutropenia, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials. Liu, J., Mi, R., Chen, L., et al.[2023]

Lenalidomide is an effective oral immunomodulator approved for treating relapsed/refractory mantle cell lymphoma (MCL) after two prior therapies, showing significant activity in various B-cell non-Hodgkin lymphomas (NHL).

Combining lenalidomide with rituximab (R2) has demonstrated promising results in both first-line and relapsed/refractory settings, and ongoing trials are evaluating its use in combination with immunochemotherapy regimens like R-CHOP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Witzig, TE., Nowakowski, GS., Habermann, TM., et al.[2020]

Lenalidomide is an FDA-approved immunomodulatory drug effective in treating bortezomib-resistant mantle-cell lymphoma and shows promise in various other lymphoma subtypes.

Its mechanism of action involves enhancing immune responses, such as T-cell and NK-cell activity, and ongoing clinical trials are focused on identifying biomarkers to improve its integration into lymphoma treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. Kritharis, A., Coyle, M., Sharma, J., et al.[2021]

In a phase II trial involving 217 patients with relapsed or refractory aggressive non-Hodgkin's lymphoma, lenalidomide demonstrated an overall response rate of 35%, with 13% achieving complete remission and 22% achieving partial remission.

Lenalidomide was found to be well tolerated, although myelosuppression was a common side effect, particularly with grade 4 neutropenia occurring in 17% of patients, indicating that while effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Witzig, TE., Vose, JM., Zinzani, PL., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide in diffuse large B-cell lymphoma. [2021]

6. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of lenalidomide in diffuse large B-cell lymphoma: a meta-analysis of randomized controlled trials. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. [2021]

9. England pubmed.ncbi.nlm.nih.gov

An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. [2022]