Epcoritamab for Chronic Lymphocytic Leukemia and Richter Syndrome

Overseen By Adrian U Wiestner, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new treatment, epcoritamab, works for individuals with chronic lymphocytic leukemia (a type of blood cancer) and Richter syndrome. Researchers aim to understand the effects of epcoritamab by analyzing samples from participants' lymph nodes, bone marrow, and blood. The goal is to observe how this treatment interacts with the body and to advance its potential as a cancer immunotherapy. This trial is by invitation only and targets individuals already being screened for a related study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that epcoritamab is likely to be safe for humans?

Research shows that epcoritamab is actively studied for its safety and effectiveness. In earlier studies, some patients with chronic lymphocytic leukemia (CLL) and Richter syndrome responded well to this treatment. Epcoritamab, also known as EPKINLY™, is an antibody therapy that helps the immune system attack cancer cells.

Regarding safety, earlier research indicates that epcoritamab is generally well-tolerated. Some patients experienced side effects, but these are often manageable. Common side effects include fever, tiredness, and reactions at the injection site. Serious side effects can occur, but they are less common. It's important to note that this treatment is still in early testing stages, so ongoing studies are essential to fully understand its safety.

Considering joining a trial? Discussing the potential risks and benefits with a healthcare provider can help in making an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic lymphocytic leukemia and Richter syndrome, which often include chemotherapy and targeted therapies like BTK inhibitors, epcoritamab introduces a novel mechanism of action. Epcoritamab is a bispecific antibody that simultaneously engages T-cells and tumor cells, prompting the immune system to directly attack cancerous cells. This innovative approach could potentially offer a more precise and effective treatment with the possibility of fewer side effects compared to traditional therapies. Researchers are particularly excited about epcoritamab's potential to improve outcomes for patients who may not respond well to existing treatments.

What evidence suggests that epcoritamab might be an effective treatment for chronic lymphocytic leukemia and Richter syndrome?

Research shows that epcoritamab, which participants in this trial will receive, yields promising results for treating chronic lymphocytic leukemia (CLL) and Richter syndrome. Studies have found that many patients, particularly those with severe conditions, respond well to this treatment. In some cases, epcoritamab significantly reduces the disease. The treatment is generally safe and well-tolerated by patients. These findings suggest that epcoritamab could be a valuable option for people with these challenging conditions. ^{1 3 4 5 6}

Who Is on the Research Team?

Adrian U Wiestner, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is specifically for individuals with certain blood cancers, including Chronic Lymphocytic Leukemia and Richter Syndrome. Participants are being invited to join the study, which will involve close monitoring of their response to a new treatment.

Inclusion Criteria

I can understand and am willing to sign the consent form.

I am willing and able to follow the study rules and attend all required visits.

Must be undergoing screening for GCT3013-03

Exclusion Criteria

Not applicable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive epcoritamab and undergo lymph node, bone marrow, and blood sample collection for pharmacodynamic evaluation

Duration not specified

Multiple visits for sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab

Trial Overview The focus of this trial is on epcoritamab, an experimental medication designed to engage the immune system in fighting cancer. The study involves collecting samples from patients before and during treatment to understand how the drug affects cancer cells.

How Is the Trial Designed?

Group I: epcoritamab Experimental Treatment 1 Intervention

Samples from subjects receiving epcoritamab on another clinical trial GCT3013-03 will be collected.

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?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Richter transformation (RT) occurs in 2-10% of chronic lymphocytic leukemia (CLL) patients and is often associated with a poor prognosis, particularly following therapy, with significant molecular changes such as TP53 inactivation in 50-60% of cases.

Despite the understanding of RT's molecular pathogenesis, patient outcomes have not significantly improved; however, there are now numerous clinical trials exploring new drugs and combinations specifically for RT, addressing a critical unmet need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Richter Transformation in Chronic Lymphocytic Leukemia: Update in the Era of Novel Agents. Tadmor, T., Levy, I.[2021]

Richter transformation (RT) is a serious complication of chronic lymphocytic leukemia (CLL) that significantly worsens survival rates, with overall survival dropping to just 3-4 months for patients who have progressed on BTK or BCL2 inhibitors.

Novel therapeutic agents targeting BTK, BCL2, and the PD1-PDL1 axis show promise in potentially improving outcomes for patients with RT, highlighting the need for randomized clinical trials to better understand their efficacy and identify which patients may benefit most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Richter transformation-is there light at the end of this tunnel? Eyre, TA.[2023]

Richter transformation (RT) is a serious complication of chronic lymphocytic leukemia (CLL) that leads to aggressive lymphoma and is diagnosed through clinical findings and confirmed by tissue biopsy.

Current treatment for RT primarily involves chemoimmunotherapy, with ongoing research into newer therapies like CAR-T cell therapy and bispecific antibodies, which may improve outcomes for patients in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Richter Transformation of Chronic Lymphocytic Leukemia-Are We Making Progress? Audil, HY., Kosydar, SR., Larson, DP., et al.[2023]

Richter syndrome (RS), a high-grade transformation of chronic lymphocytic leukaemia, is a chemotherapy-resistant condition with a poor prognosis, showing a median overall survival of only about 8 months, particularly affecting elderly and immunosuppressed patients.

Emerging treatments, including second-generation Bruton tyrosine kinase inhibitors like acalabrutinib and novel monoclonal antibodies, may offer new hope for improving outcomes in RS, highlighting the need for ongoing clinical trials and precision medicine approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update for Richter syndrome - new directions and developments. Eyre, TA., Schuh, A.[2022]

Richter syndrome (RS) occurs in 0.5-1% of chronic lymphocytic leukemia (CLL) patients per year and is often linked to a poor prognosis, with 80% of cases being clonally related to the prior CLL.

Current treatments for RS, including modern immunochemotherapy, show low response rates, but promising strategies such as stem-cell transplantation and novel immunotherapies are being explored to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Richter Syndrome: Diagnostic and Therapeutic Management]. Croizier, C., Guièze, R.[2021]

In a phase 2 study involving 9 patients with Richter's Syndrome, high-dose blinatumomab treatment led to a reduction in nodal disease in 4 patients, including one who achieved a durable complete response lasting over a year.

The treatment was well tolerated with no severe cytokine release syndrome and only one case of reversible grade 3 neurotoxicity, suggesting it is a safe option for patients with this aggressive form of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase two study of high dose blinatumomab in Richter's syndrome. Thompson, PA., Jiang, X., Banerjee, P., et al.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/883/531051/Epcoritamab-Monotherapy-in-Patients-Pts-with

Epcoritamab Monotherapy in Patients (Pts) with Relapsed or ... Epcoritamab has shown promising single-agent efficacy in both R/R CLL and Richter's syndrome in early data from EPCORE CLL-1 (phase 1b/2; ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04623541

NCT04623541 | Safety and Efficacy Study of Epcoritamab ... The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12439272/

A Case Report in an Elderly Patient This case highlights the potential of epcoritamab as an important treatment option for elderly patients with refractory DLBCL‐RS. Keywords: ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024012746

CLL-280 Epcoritamab Induces Deep Responses in ... Epcoritamab showed encouraging efficacy with a consistent safety profile in a high-risk RT cohort. Response rates were notably higher in patients without prior ...

5. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=GCT3013-03

Safety and Efficacy Study of Epcoritamab in Subjects With ... The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20).

6. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_13685.safety-and-efficacy-study-of-epcoritamab-in-subjects-with-relapsed-refractory-chronic-lymphocytic-leukemia.html

Safety and Efficacy Study of Epcoritamab in Subjects With ... The trial is an open-label, multi-center satefy and efficacy trial of epcoritamab in relapsed/refractory chronic lymphocytic leukemia (R/R ...