AzTrials
AzTrials

Recurrent Diffuse Large B-Cell LymphomaPhase 1/2NCT06536049

Epcoritamab Plus Ibrutinib for the Treatment of Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

A Phase 1/2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Grade 3b Follicular Lymphoma, run by Yazeed Sawalha at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase Ib/II trial evaluates the safety, optimal dose, and efficacy of the combination of epcoritamab and ibrutinib in treating patients with aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or responded to previous treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
3 sitesUnited States
Study dates
2 Apr 2025to 31 Oct 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • One of the following CD20+ B-cell non-Hodgkin lymphoma subtypes (note, documentation of CD20 positivity by flow cytometry and/or immunohistochemistry is based on any representative pathology report)
  • Diffuse large B-cell lymphoma (DLBCL), including DLBCL, not otherwise specified (NOS); T-cell/histiocyte-rich large B-cell lymphoma; and Epstein-Barr virus-positive DLBCL, NOS
  • High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma) or HGBL, NOS
  • Primary mediastinal B-cell lymphoma (PMBCL)
  • Follicular lymphoma, grade 3b (also known as follicular large B-cell lymphoma in the 5th edition of World Health Organization [WHO] classification of lymphoid neoplasms)
  • Patients with previously diagnosed indolent lymphoma (follicular lymphoma or marginal zone lymphoma but not lymphoplasmacytic lymphoma or small lymphocytic lymphoma/chronic lymphocytic leukemia) who have transformed to any of the above lymphoma subtypes are eligible
Show all 26Show fewer
  • Patients must have relapsed or refractory aggressive B-cell lymphoma and received prior treatment with an anthracycline in combination with an anti-CD20 monoclonal antibody:
  • ≥ 2 prior systemic lymphoma treatments OR
  • ≥ 1 prior systemic lymphoma treatment in patients with high-risk disease defined as primary refractory or relapsed within 12 months of completing anthracycline-based frontline treatment who are ineligible for chimeric antigen receptor (CAR) T cells per the treating physician. The reason for CAR T-cell treatment ineligibility should be documented
  • Prior treatment with a BTK inhibitor is allowed if stopped due to lymphoma progression or treatment completion but not intolerance
  • Prior treatment with autologous stem cell transplant (ASCT) is allowed if ≥ 100 days prior to enrollment
  • Prior treatment with CAR T cells is allowed if ≥ 30 days prior to enrollment
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ibrutinib or epcoritamab in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Measurable disease (defined as > 1.5 cm in diameter) or at least one PET fludeoxyglucose F-18 (FDG) avid area of disease
  • Absolute neutrophil count (ANC) ≥ 1,000/mcL
  • Platelet count ≥ 75,000/mcL. Platelet count ≥ 50,000/mcL is allowed in case of bone marrow involvement and/or splenomegaly
  • Hemoglobin ≥ 8 g/dL
  • Transfusion and/or growth factor support within 7 days (or 14 days in case of long-acting growth factors such as pegylated granulocyte colony-stimulating factor [G-CSF]) of enrollment to meet these requirements is not permitted
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN) (unless due to Gilbert's disease or hemolysis in which case bilirubin must be < 3 x ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 3 x institutional ULN
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 3 x institutional ULN
  • Creatinine clearance > 45 mL/min calculated by Cockcroft-Gault. Patients on dialysis are not eligible
  • The effects of ibrutinib and epcoritamab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 2 weeks before initiation of treatment, for the duration of study participation and for 12 months after completing treatment. Should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately. Men must agree to refrain from sperm donation for at least 12 months after the last dose of epcoritamab
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Patients must have the ability to understand and the willingness to sign a written informed consent document and Health Insurance Portability and Accountability Act (HIPAA) consent document. Voluntary written consent must be given before the performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Who cannot join

  • Prior therapy with a bispecific antibody targeting CD3 and CD20
  • Prior lymphoma therapy should be completed greater than two weeks before the start of protocol therapy, except for corticosteroids used for palliation of symptoms
  • Patients who require immediate cytoreductive therapy for their lymphoma per the treating physician's assessment are ineligible
  • Patients with a history of allogeneic stem cell transplantation are excluded unless the transplant was > 180 days before the first scheduled dose of ibrutinib AND the patient does not have evidence of active acute or chronic graft versus host disease AND the patient must not have taken immunosuppressive medications associated with the transplant for at least 1 month before the first scheduled dose of ibrutinib
  • Ongoing systemic treatment with a strong CYP3A inhibitor or inducer. Treatment with any strong CYP3A inhibitor or inducer needs to be stopped for 5 half-lives prior to starting treatment on trial
  • Major surgery within 4 weeks before the start of treatment other than surgery performed for lymphoma diagnosis
Show all 24Show fewer
  • Known active central nervous system (CNS) involvement by lymphoma. Patients who are enrolled and subsequently identified to have pathologic confirmation of CNS involvement by lymphoma may be continued on the study at the discretion of the principal investigator
  • Active uncontrolled infection or infection requiring intravenous (IV) antibiotic therapy for > 2 consecutive days within 2 weeks prior to the first dose of study drug
  • Evidence of current uncontrolled or symptomatic cardiovascular conditions, including, uncontrolled cardiac arrhythmias, history of or symptomatic congestive heart failure (New York Heart Association [NYHA] class III or greater), unstable angina, or myocardial infarction within the past 6 months. Poorly controlled or clinically significant atherosclerotic vascular disease including angioplasty, cardiac or vascular stenting within 6 months of enrollment
  • Known liver cirrhosis with moderate to severe hepatic impairment (Child-Pugh class B or C)
  • Clinically significant pulmonary disease or history of bronchospasm requiring intubation, or clinically significant active interstitial lung disease or pneumonitis
  • History of cerebrovascular accident or transient ischemic attack within the 6 months before day 1, cycle 1 of treatment
  • Any prior history of intracranial hemorrhage
  • Clinically significant known bleeding diatheses or platelet dysfunction disorders.
  • Receiving treatment with coumadin/warfarin
  • Known gastrointestinal disease or gastrointestinal procedure that will significantly interfere with the oral absorption or tolerance of ibrutinib including the inability to swallow pills/capsules
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
  • Prior solid organ transplant
  • History of other malignancies that could affect compliance with the protocol or interpretation of results in the opinion of the investigator
  • Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 21 days of the first scheduled dose of ibrutinib (cycle 1 day -7)
  • Known history of HIV, active hepatitis C infection (HCV ribonucleic acid [RNA] polymerase chain reaction [PCR]-positive) and/or active hepatitis B infections (HBV DNA PCR-positive). If hepatitis B core (HBc) antibody is positive, the patient must be evaluated for the presence of HBV DNA by PCR. If HCV antibody is positive, the patient must be evaluated for the presence of HCV RNA by PCR. Patients with positive HBc antibody and negative HBV DNA by PCR are eligible. Patients with positive HCV antibody and negative HCV RNA by PCR are eligible
  • Pregnant or breastfeeding women are excluded from this study. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with ibrutinib or epcoritamab, breastfeeding should be discontinued if the mother is treated with ibrutinib or epcoritamab
  • Patients with ongoing clinically significant grade ≥ 2 toxicity from prior therapy

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

The Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCClinicaltrials@osumc.edu

United States3 sites, 3 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Yazeed Sawalha, 614-293-0837, Yazeed.sawalha@osumc.edu

    Yazeed Sawalha

    Recruiting

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

    Alisha Seay, seayx020@umn.edu

    Marie Hu

    Recruiting

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

    Massey CTO Lymphoma/Myeloma Team, 804-628-6430, masseyhemmlg@vcu.edu

    Bruce Hough, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase Ib/II Trial of Epcoritamab Plus Ibrutinib in Patients With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma

This phase Ib/II trial evaluates the safety, optimal dose, and efficacy of the combination of epcoritamab and ibrutinib in treating patients with aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to two different types of receptors (proteins present on the cell surface) at the same time. The two receptors that epcoritamab binds to are called CD3 and CD20. CD3 is found on T cells, which are important cells of the immune system that help fight cancer and infections. CD20 is found on the surface of most types of aggressive B-cell non-Hodgkin lymphoma cells. By binding to both CD3 and CD20, epcoritamab brings the two cells close together so the T cells can fight and kill the lymphoma B cells. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, binds to a protein on B cells, a type of white blood cell from which the lymphoma developed. By doing this it decreases the ability of the lymphoma B cells to survive and grow. Ibrutinib may also improve the health (or fitness) of T cells thus making epcoritamab safer and/or more effective.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the recommended phase II dose (RP2D) and safety of epcoritamab plus ibrutinib.

II. Determine the rate and severity of cytokine release syndrome (CRS).

SECONDARY OBJECTIVES:

  1. Determine the complete response (CR) rate (Lugano 2014) after cycle 12 or the last dose of treatment if stopped earlier.

II. Determine the overall response rate (ORR) (CR + partial response [PR]) (Lugano 2014), progression-free survival (PFS), duration of response (DOR), and overall survival (OS) of patients treated at the RP2D.

III. Determine the best ORR and CR rate (Lugano 2014).

EXPLORATORY OBJECTIVES:

  1. Characterize cytokine profile following ibrutinib and epcoritamab and explore whether levels of cytokine production correlate with both the appearance of CRS and ORR.

II. Analyze peripheral blood mononuclear cells collected pre-ibrutinib, pre-epcoritamab, and throughout treatment using spectral flow cytometry to assess the effect of ibrutinib on T-cell numbers and function.

III. Examine tumor samples attained before starting treatment and at relapse and explore aspects of the microenvironment that may contribute to epcoritamab failure.

IV. Measure circulating tumor deoxyribonucleic acid (DNA) (ctDNA) to correlate its presence with response by positron emission tomography (PET) imaging and track the emergence of treatment-resistant clones.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days -7 to 28 of cycle 1 and on days 1 to 28 of remaining cycles, as well as epcoritamab subcutaneously (SC) on days 1, 8, 15 and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and on day 1 of remaining cycles. Treatment repeats every 28 days for up to 6 cycles of ibrutinib and up to 12 cycles of epcoritamab in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, computed tomography (CT) and PET/CT throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study.

After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for up to 5 years.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Epcoritamab
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow aspiration and biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT and PET/CT

  • EpcoritamabBiological

    Also called Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, Epkinly

    Given SC

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765

    Given PO

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

Study groups in NCT06536049
Study groupRoleWhat they receive
Treatment (epcoritamab, ibrutinib)ExperimentalPatients receive ibrutinib PO QD on days -7 to 28 of cycle 1 and on days 1 to 28 of remaining cycles, as well as epcoritamab SC on days 1, 8, 15 and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and on day 1 of remaining cycles. Treatment repeats every 28 days for up to 6 cycles of ibrutinib and up to 12 cycles of epcoritamab in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT and PET/CT throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Epcoritamab; Drug: Ibrutinib; Procedure: Positron Emission Tomography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events (AEs)

    AEs will be tabulated by type and grade using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 60 days after last dose of study drug

  2. Incidence of cytokine release syndrome (CRS)

    CRS severity will be graded using American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome criteria. The CRS rate will be calculated together with 95% one-sided confidence intervals among evaluable patients.

    Measured: Up to 60 days after last dose of study drug

Secondary outcomes (5)

  1. Overall response rate (ORR)

    ORR will be defined as the proportion of patients achieving a complete or partial response and reported with a 95% binomial confidence interval.

    Measured: Up to 24 months

  2. Complete response (CR) rate

    Measured: Up to cycle 12 (each cycle is 28 days)

  3. Progression-free survival (PFS)

    PFS will be defined for all patients who begin treatment therapy to the date of progression or death. PFS will be estimated using the method of Kaplan-Meier, where estimates at time points of interest will be reported with 95% confidence intervals. Median PFS will be evaluated if estimable.

    Measured: From the start of treatment to the time of progression or death, whichever occurs first, assessed up to 5 years

  4. Duration of response (DOR)

    Measured: Up to 5 years

  5. Overall survival (OS)

    OS will be defined for all patients who begin treatment therapy to the date of death from any cause. OS will be estimated using the method of Kaplan-Meier, where estimates at time points of interest will be reported with 95% confidence intervals. Median OS will be evaluated if estimable.

    Measured: From the start of treatment to death from any cause, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2024
  2. Study start2 Apr 2025
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06536049
Sponsor's protocol ID
OSU-23364
Other IDs
NCI-2024-05519
Status last verified
Aug 2026
First submitted
31 Jul 2024
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Grade 3b Follicular Lymphoma, run by Yazeed Sawalha at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) (time frame: Up to 60 days after last dose of study drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06536049.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in