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AzTrials

Relapsed Large B-cell LymphomaPhase 2NCT06811272

Outpatient Epcoritamab in Large B-cell Lymphoma

A Phase 2 study testing Epcoritamab, Rituximab combined with cyclophosphamide, vincristine, and prednisone and Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone in people with Relapsed Large B-cell Lymphoma and Refractory Large B-cell Lymphoma, run by Massachusetts General Hospital at 2 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

The purpose of this study is to measure the efficacy of the study drug, epcoritamab, in participants with relapsed/refractory large B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Epcoritamab, Rituximab combined with cyclophosphamide, vincristine, and prednisone and Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
5 Jun 2025to 1 Oct 2028
Phase
Phase 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

  • First Line Cohort
  • No prior systemic antineoplastic therapy for large B-cell lymphoma.
  • Score of "frail" or "unfit" on Fondazione Italiana Linfomi simplified Geriatric Assessment (FIL sGA) (Appendix E).
  • Second Line Cohort
  • Relapsed or refractory disease treated with 1 prior systemic antineoplastic line of therapy that includes an anti-CD20 monoclonal antibody plus an anthracycline and/or an alkylating agent. Patients who have received more than 1 prior systemic antineoplastic line of therapy are not eligible.
  • Not a candidate for high dose chemotherapy and autologous stem cell transplant per the treating investigator, or patient refusal of high dose chemotherapy and autologous transplant.
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  • Both Cohorts
  • Participants must have large B-cell lymphoma of one of the following histologic subtypes by WHO criteria:
  • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS)
  • High grade B-cell lymphoma (HGBCL) with rearrangements of MYC and BCL2 and/or BCL6
  • HGBCL NOS
  • EBV+ DLBCL
  • Primary mediastinal B-cell lymphoma
  • T-cell/histiocyte rich LBCL
  • Grade 3B follicular lymphoma
  • Large B-cell lymphoma transformed from underlying indolent NHL
  • PET measurable disease per Lugano criteria (Section 10).
  • Age ≥18 years.
  • ECOG performance status 0-2 (Appendix A)
  • Participants must meet the following organ and marrow function as defined below:
  • absolute neutrophil count ≥1,000/mcL (Growth factor support as clinically indicated is permitted)
  • platelets ≥75,000/mcL (>50,000 in the presence of bone marrow involvement or splenomegaly; platelet transfusions as clinically indicated are permitted)
  • Hemoglobin ≥8 g/dL (>7 g/dL in the presence of bone marrow involvement; blood transfusions as clinically indicated are permitted)
  • Participants must have adequate organ function as defined below (unless abnormalities are considered related to target organ involvement or compression by lymphoma):
  • total bilirubin ≤ 1.5x institutional upper limit of normal (ULN) (Isolated bilirubin ≤3.0x ULN is acceptable if considered secondary to Gilbert's syndrome)
  • AST(SGOT) and ALT(SGPT) ≤3.0x institutional ULN
  • Creatinine clearance ≥40 mL/min eGFR (Cockcroft-Gault or MDRD equation)
  • PT within institutional normal range (unless on anticoagulation expected to affect PT, in which case PT cut off does not apply)
  • PTT within institutional normal range (unless on anticoagulation expected to affect PTT, in which case PTT cut off does not apply)
  • Participants with known history or current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • Ability to remain within 60 minutes of the administration site for 24 hours following cycle 1 day 15 dose of study drug.
  • The effects of epcoritamab on the developing human fetus are unknown. Women of child-bearing potential must agree to use adequate contraception starting with the first dose of study drug, for the duration of study participation, and for at least 4 months after the last dose of study intervention. Women must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Adequate contraception methods (see Appendix B for further guidance):
  • Male Partner Sterilization: When the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate.
  • Use of a combination of any two of the following (one from "a" and one from "b"):
  • Placement of an intrauterine device (IUD) or intrauterine system or established use of oral, injected, or implanted hormonal methods of contraception
  • Barrier methods of contraception: Male Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
  • True abstinence, defined as refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject.
  • Nonchildbearing potential is defined as follows:
  • ≥45 years of age and has not had menses for at least 12 consecutive months.
  • Subjects who have been amenorrhoeic for <1 year must have, on at least two occasions prior to first dose of study drug, a follicle stimulating hormone value greater than 40 IU/L; historical follicle stimulating hormone values are eligible
  • Post-bilateral oophorectomy (with or without hysterectomy) or post-tubal ligation at least six weeks prior to first dose of study drug. Documented oophorectomy can be confirmed with medical records of the actual procedure or confirmed by imaging (ultrasound or CT). Tubal ligation must be confirmed with medical records of the actual procedure. In the case of oophorectomy alone, reproductive status must be confirmed by follicle stimulating hormone level assessment as above.
  • Women of childbearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test at screening.
  • Fertile men, defined as all males physiologically capable of conceiving offspring who are sexually active with a female partner of childbearing potential, must agree to use adequate contraception starting with the first dose of study drug, for the duration of study participation, and 4 months after completion of administration. Men must also agree not to donate sperm during this period. Men may agree to remain abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term or persistent basis) OR agree to use a male condom, and their female partner must use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse if they are a WOCBP (including pregnant females). Please see Appendix B for contraception guidance.
  • Ability to understand and the willingness to sign a written informed consent document by the participant or a legally authorized representative.

Who cannot join

  • Participant must not have used an investigational drug or approved systemic lymphoma therapy within 28 days preceding the first dose of study drug. Steroids for lymphoma disease control are permitted but must be stopped at least 7 days prior to the first dose of study drug.
  • Participants must not have received prior CD20/CD3 bispecific antibody.
  • Participants must not have received prior autologous or allogeneic stem cell transplant.
  • Participants must not have received prior anti-CD19 CAR T-cell therapy.
  • Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia. At the discretion of the overall PI, participants with residual toxicities > Grade 1 may be considered eligible if in the opinion of the overall PI the residual toxicity is not likely to interfere with the safety or efficacy assessment of the investigational regimen. For residual hematologic toxicities greater than Grade 1, see 3.1.7.
  • Participants must not have known central nervous system involvement by lymphoma.
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  • Participants must not have a current life-threatening illness, medical condition, or organ system dysfunction (other than the disease under study) which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk. Patients that have mild cognitive impairment or dementia are eligible per investigators' opinion.
  • Participants must not have an uncontrolled active infection. Localized fungal infection of skin or nails are permitted.
  • Participants must not have active uncontrolled autoimmune disease. Autoimmune disease under control with chronic systemic corticosteroids at a dose of 10 mg/day of prednisone or less, or equivalent corticosteroid, are eligible.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab. A history of an infusion reaction to CD20-directed therapy is not considered an allergic reaction.
  • Women who are pregnant are excluded from this study because it is unknown if epcoritamab can cause embryo-fetal harm when administered to a pregnant woman. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with epcoritamab, breastfeeding should be discontinued if the mother is treated with epcoritamab on study.
  • Participant must not have active uncontrolled HIV infection. Participants with HIV are eligible if disease is adequately controlled on an antiretroviral regimen that is in accordance with the current international AIDS Society guidelines, with adequate control defined by presence of both an undetectable viral load, a CD4 count >350, no evidence of AIDS-defining illness (with the exception of a lymphoma diagnosis), and no active opportunistic infections (infections controlled on appropriate anti-infective therapy are permitted).
  • Participant must not have active hepatitis B infection. Participants with positive HBV core antibody or HBV surface antigen at screening are eligible if HBV viral load is negative by PCR and they are on appropriate antiviral therapy.
  • Participant must not have active hepatitis C infection. Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
  • Note: Participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
  • -Subject has no known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection or has had recent known exposure to someone with SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test, or 2 negative antigen test results at least 24 hours apart, to rule out SARS-CoV-2 infection.
  • Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/recommendations. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria: No signs/symptoms suggestive of active SARS-CoV-2 infection AND negative testing (molecular (e.g., PCR) result or 2 negative antigen test results at least 24 hours).
  • Participants must not have received a live virus vaccine within 28 days of first dose of study drug.
  • Participants must not have any known past or current malignancy other than inclusion diagnosis, except for:
  • Cervical carcinoma of Stage 1B or less.
  • Non-invasive basal cell or squamous cell skin carcinoma.
  • Non-invasive, superficial bladder cancer.
  • Prostate cancer with a current PSA level <0.1 ng/mL.
  • Any curable cancer with a complete response (CR) of >2 years duration
  • Uncontrolled seizure disorder
  • History of Progressive Multifocal Leukoencephalopathy (PML)

Trial locations and contacts

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

Julie E. Haydu, MD, PhD contact

617-724-4000

julie_haydu@mgh.harvard.edu

United States2 sites, 2 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Julie E. Haydu, MD, PhD, 617-724-4000, julie_haydu@mgh.harvard.edu

    Recruiting

  • Newton-Wellesley Hospital

    Newton, Massachusetts, 02462

    Jeffrey Barnes, MD, PhD, 617-724-4000, JABARNES@mgh.harvard.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2 Study of Outpatient Epcoritamab in Large B-cell Lymphoma

The purpose of this study is to measure the efficacy of the study drug, epcoritamab, in participants with relapsed/refractory large B-cell lymphoma.

Read the detailed description

This is a phase 2 study of outpatient administration of administration of epcoritamab in large B-cell lymphoma. The first line cohort will enroll participants with treatment-naïve large B-cell lymphoma who are "frail" and/or medically "unfit" on a standardized assessment. The second line cohort will enroll non-transplant eligible large B-cell lymphoma that has relapsed after, or is refractory to, 1 prior line of therapy.

Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has approved epcoritamab as a treatment option for your disease after at least two prior treatments.

The study treatment may continue for up to 24 cycles or until disease progression, unacceptable toxicity, or withdrawal. Participants will be followed for up to 24 months after last dosage of epcoritamab, or until disease progression or withdrawal, whichever occurs first. After 24 months or at time of progression, participants may be followed annually for survival status.

It is expected that about 30 people will take part in this research study.

Being tested
Epcoritamab, Rituximab combined with cyclophosphamide, vincristine, and prednisone, Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone, Rituximab combined with polatuzumab, cyclophosphamide, doxorubicin, and prednisone
Keywords
Non-Transplant Eligible, Second Line Therapy, DLBCL, HGBCL, Naïve large B-cell lymphoma, First Line Therapy

What participants receive

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

  • EpcoritamabDrug

    Bispecific IgG1 antibody

  • Rituximab combined with cyclophosphamide, vincristine, and prednisoneDrug

    Epco-R-CVP

  • Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisoneDrug

    Epco-R-CHOP

  • Rituximab combined with polatuzumab, cyclophosphamide, doxorubicin, and prednisoneDrug

    Epco-pola-R-CHP

Study groups in NCT06811272
Study groupRoleWhat they receive
First LineExperimentalEpcoritamab will be given as monotherapy on EPCO cycles 1 days 1, 8, 15, and 22, EPCO cycles 2 days 1, 8, 15, and 22, EPCO cycles 3-4 days 1 and 15, and EPCO cycles 3-8 days 1 and 15 as an injection under your skin (subcutaneous injection). Epcoritamab will be given with chemotherapy through the vein with steroid pills (prednisone) on EPCO-CHEMO cycles 1-4 day 1 and EPCO-CHEMO cycles 1-6 day 1 based on tumor response. There are three different chemotherapy regimens which are Epco-R-CVP, Epco-R-CHOP, and Epco-pola-R-CHP. Epco-R-CVP consists of epcoritamab, rituximab, cyclophosphamide, vincristine, and prednisone. Epco-R-CHOP consists of epcoritamab, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Epco-pola-R-CHP consist of epcoritamab, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone. You will receive dexamethasone which may provide relief for areas of the body that are inflamed during study treatment.
Receives: Drug: Epcoritamab; Drug: Rituximab combined with cyclophosphamide, vincristine, and prednisone; Drug: Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone; Drug: Rituximab combined with polatuzumab, cyclophosphamide, doxorubicin, and prednisone
Second LineExperimentalEpcoritamab will be given as an injection under the skin (subcutaneous injection) on cycle 1-3 days 1, 8, 15, and 22, cycle 4-9 days 1 and 15, and cycle 10 and onwards day 1. You will receive dexamethasone which may provide relief for areas of the body that are inflamed during study treatment.
Receives: Drug: Epcoritamab

What is being measured

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

  1. Complete Response Rate (CRR) in first line cohort

    The CRR is defined as the proportion of subjects achieving an objective response of complete response (CR) according to the Lugano Classification, prior to start of another non-study anticancer therapy. CRR is based on the best overall response. CRR will be reported as a proportion, exact binomial confidence interval, and assessed using an exact binomial test.

    Measured: Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 12 months after initial dose of study treatment.

  2. 12-month progression free survival (PFS) in second line cohort

    The time from registration to the earlier of progression or death due to any cause and will be defined as the percent of patients alive and progression-free at 12 months. Participants alive without disease progression are censored at date of last disease evaluation.

    Measured: Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 12 months after initial dose of study treatment.

Secondary outcomes (12)

  1. 12-month progression free survival (PFS) in first line cohort

    PFS is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. The 12-month PFS rate will be reported as a proportion, exact binomial confidence interval, and assessed using an exact binomial test

    Measured: Day 1 to 24 months post treatment

  2. Complete Response Rate in second line cohort

    The proportion of subjects achieving an objective response of complete response (CR) according to the Lugano Classification, prior to start of another non-study anticancer therapy.

    Measured: Day 1 to 24 months post treatment

  3. Overall Response Rate

    The proportion of subjects achieving an objective response of complete response (CR) or partial response (PR) according to the Lugano Classification, prior to start of another non-study anticancer therapy.

    Measured: Day 1 to 24 months post treatment

  4. Median Duration of Response

    The time from first response to disease progression or death, and will be summarized using Kaplan-Meier estimates.

    Measured: Date of first response to first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months post treatment

  5. Median Duration of Complete Response

    The time subjects achieve complete response to disease progression or death and will be estimated using Kaplan Meier method or cumulative incidence curves.

    Measured: Date of complete response to first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months post treatment

  6. Overall Survival

    The time from registration to death due to any cause or censored at date last known alive and will be summarized using Kaplan-Meier estimates.

    Measured: Registration date to date of death from any cause or last known alive date, assessed up to 24 months post treatment

  7. Incidence and Severity of Treatment-Emergent Adverse Events

    Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All participants will be followed and assessed for safety and tolerability of the protocol therapy.

    Measured: Day 1 to 24 months post treatment

  8. Median Time to Resolution of Cytokine Release Syndrome

    The duration of time for subjects to resolve cytokine release syndrome (CRS) and will be estimated using Kaplan Meier method or cumulative incidence curves.

    Measured: Date of cytokine release syndrome to resolution date of cytokine release syndrome

  9. Median Time to Resolution of Immune Effector Cell-Associated Neurotoxicity Syndrome

    The duration of time for subjects to resolve immune effector cell-associated neurotoxicity syndrome (ICANS) and will be estimated using Kaplan Meier method or cumulative incidence curves.

    Measured: Date of immune effector cell-associated neurotoxicity syndrome to resolution date of immune effector cell-associated neurotoxicity syndrome

  10. Proportion of Subjects Receiving Interventions for CRS and/or ICANS

    The number of subjects receiving interventions for CRS and ICANS, CRS, or ICANS and will be estimated using Kaplan Meier method or cumulative incidence curves.

    Measured: Date of intervention for CRS and/or ICANs to resolution of CRS and/or ICANS

  11. Rate of Hospitalization

    The frequency of subjects that are hospitalized and will be estimated using Kaplan Meier method or cumulative incidence curves.

    Measured: Day 1 to 24 months post treatment

  12. Rate of Emergency Room Visits

    The frequency of subjects that go to the emergency room and will be estimated using Kaplan Meier method or cumulative incidence curves.

    Measured: Day 1 to 24 months post treatment

Timeline

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

  1. First posted6 Feb 2025
  2. Study start5 Jun 2025
  3. Primary completion1 Oct 2026 (estimated)
  4. Study completion1 Oct 2028 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06811272
Sponsor's protocol ID
25-006
Status last verified
Jul 2026
First submitted
31 Jan 2025
Last updated
13 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Julie E. Haydu, MD, PhD (julie\_haydu@mgh.harvard.edu) at 617-724-4000. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Epcoritamab, Rituximab combined with cyclophosphamide, vincristine, and prednisone and Rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone in people with Relapsed Large B-cell Lymphoma and Refractory Large B-cell Lymphoma, run by Massachusetts General Hospital at 2 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 45 inclusion and 26 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 13 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 2 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 phase mean?

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 Julie E. Haydu, MD, PhD (617-724-4000, julie_haydu@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response Rate (CRR) in first line cohort (time frame: Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 12 months after initial dose of study treatment.). 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 NCT06811272.

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 13 Aug 2026.

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