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Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedPhase 2NCT06238648

Epcoritamab Compared to Observation for Treating B-cell Lymphoma Patients Not in Complete Remission After CD19-directed CAR-T Therapy

A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Diffuse Large B-Cell Lymphoma, Not Otherwise Specified and Primary Mediastinal Large B-Cell Lymphoma, run by Academic and Community Cancer Research United at 6 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 II trial compares epcoritamab to standard practice (observation) for the treatment of patients with B-cell lymphomas who are not in complete remission after treatment with CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Epcoritamab is a bispecific antibody. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
6 sitesUnited States
Study dates
31 Jan 2024to 31 Dec 2030
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

  • Men and women >= 18 years of age
  • Documented histological confirmation of diffuse large b-cell lymphoma not otherwise specified [DLBCL NOS], primary mediastinal large b-cell lymphoma (LBCL), or transformations of indolent B-cell lymphomas, according to the 5th edition of World Health Organization (WHO) classification of lymphoid neoplasms, with CD20 positivity as determined by assessment of tumor cells =< 6 months prior to registration pre- CAR-T biopsy specimen by immunohistochemistry or flow cytometry
  • Patients treated with the commercially available CD19-directed CAR-T products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel), and who have a partial response at day 30 +/- 7 days PET- CT assessment based on Lugano criteria (Deauville score of 4 or 5)
  • Documented measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2. (Form is available on the Academic and Community Cancer Research United [ACCRU] web site under Study Resources -> Forms)
  • Absolute neutrophil count (ANC) >= 1,000/mm^3, granulocyte colony stimulating factor (G-CSF) allowed (obtained =< 14 days prior to registration)
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  • Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)
  • Hemoglobin >= 7.0 g/dL if asymptomatic or hemoglobin > 8 if symptomatic; transfusion support allowed, if necessary (obtained =< 14 days prior to registration)
  • NOTE: symptoms include shortness of breath, fatigue, lightheadedness
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin or lymphoma involvement of the liver and total bilirubin is =< 5 x ULN (obtained =< 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =< 14 days prior to registration)
  • Calculated creatinine clearance must be >= 45 mL/min using the Crockcroft- Gault formula (obtained =< 14 days prior to registration)
  • NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms."
  • Negative serum pregnancy test done =< 7 days prior to registration for a woman of childbearing potential (WOCBP) only
  • NOTE: A WOCBP is a sexually mature female who:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Provide informed written consent =< 28 days prior to registration
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study, i.e., active treatment and clinical follow-up)
  • Willing to provide mandatory tissue specimens and blood specimens for correlative research purposes

Who cannot join

  • Patients post CAR-T who have bulky disease defined as a disease focus >= 7.5cm in diameter at day 30 +/- 7 days PET-CT assessment
  • Patients post CAR-T who have progressive disease, stable disease or complete response at day 30 +/- 7 days PET-CT assessment based on Lugano criteria
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effect on the developing fetus and newborn are unknown
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception (men and women)
Show all 28Show fewer
  • Any of the following prior therapies:
  • CD20xCD3 bispecific antibody at any point prior to registration
  • CD20-targeted monoclonal antibody (e.g., rituximab, obinutuzumab or biosimilars) =< 4 weeks prior to registration
  • Ongoing cytokine release syndrome (CRS) or neurotoxicity post CAR-T
  • Prior grade 4 CRS or neurotoxicity after most recently administered CAR-T
  • Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening and based on clinical symptoms, MRI, or lumbar puncture
  • Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection requiring systemic treatment (excluding prophylactic treatment) =< 14 days prior to registration, including COVID- 19 infection.
  • NOTE: If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable and on suppressive therapy.
  • NOTE: If history of treated hepatitis C virus (HCV) infection, HCV viral load must be undetectable.
  • NOTE: Patients known to be human immunodeficiency virus (HIV) positive, but stable on anti-retroviral therapy with an undetectable HIV viral load pre-CART, are eligible for this trial.
  • NOTE: Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
  • NOTE: Past COVID-19 infection may be a risk factor, but if resolved symptoms and the subject is vaccinated, they may be enrolled
  • Symptomatic congestive heart failure (New York Heart Association [NYHA] class 3 or 4)
  • Unstable angina pectoris
  • Unstable cardiac arrhythmia present =< 14 days prior to registration
  • Psychiatric illness/social situations that would limit compliance with study requirement
  • History or presence of CNS disorder such as seizure disorder (not including resolved childhood febrile seizures), cerebrovascular ischemia/hemorrhage (not including transient ischemic attacks), cerebellar disease, or any autoimmune disease with CNS involvement
  • Receiving any other investigational agent which would be considered treatment for the primary neoplasm =< 14 days prior to registration
  • Other active malignancy requiring therapy < 2 years prior to registration (localized non-melanoma skin cancer is allowed)
  • Clinically significant cardiovascular disease, including: Myocardial infarction within 1 year prior to randomization, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association class III-IV) cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0 grade 2 or higher), or clinically significant electrocardiogram (ECG) abnormalities

Trial locations and contacts

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

6 sites in 1 country

United States6 sites, 6 recruiting

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

    Natalie S. Grover, natalie_grover@med.unc.edu

    Natalie S. Grover

    Not yet recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Lori Leslie, Lori.Leslie@hmhn.org

    Lori Leslie

    Not yet recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Miguel-Angel Perales, peralesm@mskcc.org

    Miguel-Angel Perales

    Not yet recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    ACCRU Operations, 507-538-7448, ACCRU@mayo.edu

    Grzegorz S. Nowakowski

    Not yet recruiting

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

    Allison Bock, allison.bock@hci.utah.edu

    Allison Bock

    Recruiting

  • Siteman Cancer Center at Washington University

    St Louis, Missouri, 63110

    Dilan A. Patel, dpatel1@wustl.edu

    Dilan A. Patel

    Not yet recruiting

Other trials in United States

About this study

Official title: Multicenter, Randomized Phase II Study of Epcoritamab for Patients With Aggressive B-Cell Lymphomas Achieving a Partial Response After CD19-Directed CAR-T Therapy

This phase II trial compares epcoritamab to standard practice (observation) for the treatment of patients with B-cell lymphomas who are not in complete remission after treatment with CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Epcoritamab is a bispecific antibody. It works by simultaneously attaching to a molecule called CD20 on cancerous B-cells and a molecule called CD3 on effector T-cells, which are a type of immune cell. When epcoritamab binds to CD20 and CD3, it brings the two cells together and activates the T-cells to kill the cancerous B-cells. Epcoritamab may increase a patient's chances of achieving complete remission after CD19-directed CAR-T therapy, compared to standard observation.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To compare complete response (CR) rate using the Lugano 2014 criteria for patients receiving epcoritamab versus observation alone in patients with aggressive B-cell lymphomas who achieved partial response (PR) post CAR-T therapy.

SECONDARY OBJECTIVES:

  1. To compare the progression free survival (PFS) of epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

II. To compare event free survival (EFS) in patients who receive epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

III. To compare the overall survival (OS) of epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

IV. To compare the duration of response (DOR) of epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

  1. To compare the duration of complete response (DoCR) of epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

VI. To compare the time to response (TTR) of epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

VII. To compare the objective response rate (ORR) of epcoritamab determined by Lugano 2014 versus observation alone in patients with aggressive B-cell lymphomas post CAR-T.

VIII. To assess the safety and tolerability of epcoritamab post CAR-T in patients with aggressive B-cell lymphomas.

EXPLORATORY OBJECTIVE:

  1. To assess outcomes based on CAR-T line of therapy and costimulatory domain of CAR-T construct.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive epcoritamab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and day 1 of cycles 10-12. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) at screening, undergo positron emission tomography (PET)/computed tomography (CT) and collection of blood samples throughout the trial, and undergo biopsy at screening and end of treatment. Patients may undergo CT or MRI during follow up.

ARM B: Patients undergo observation per standard care. Patients also undergo MRI at screening, undergo PET/CT and collection of blood samples throughout the trial, and undergo biopsy at screening and end of treatment. Patients may undergo CT or MRI during follow up.

After completion of study treatment, patients are followed up every 90 days for 1 year and then every 180 days for up to 5 years post-registration.

Being tested
Biopsy, Biospecimen Collection, Computed Tomography, Epcoritamab, Magnetic Resonance Imaging
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.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood samples

  • Computed TomographyProcedure or surgery

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

    Undergo PET/CT and/or CT

  • EpcoritamabBiological

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

    Given SC

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • Patient ObservationOther

    Also called Active Surveillance, deferred therapy, expectant management, Observation

    Undergo observation

  • 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 NCT06238648
Study groupRoleWhat they receive
Arm A (epcoritamab)ExperimentalPatients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and day 1 of cycles 10-12. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening, undergo PET/CT and collection of blood samples throughout the trial, and undergo biopsy at screening and end of treatment. Patients may undergo CT or MRI during follow up.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Epcoritamab; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography
Arm B (observation)Active comparatorPatients undergo observation per standard care. Patients also undergo MRI at screening, undergo PET/CT and collection of blood samples throughout the trial, and undergo biopsy at screening and end of treatment. Patients may undergo CT or MRI during follow up.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Other: Patient Observation; Procedure: Positron Emission Tomography

What is being measured

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

  1. Objective status of complete response (CR)

    CR will be assessed using Lugano 2014 criteria. Complete response rate is defined as the number of patients who achieve objective status of CR divided by the total number patients in each arm. Primary analysis population will be used for this endpoint. The proportion of CR rate in each arm with corresponding confidence interval and p-value comparing the CR rate will be reported.

    Measured: From randomization up to one year

Secondary outcomes (8)

  1. Progression free survival

    Disease progression will be defined by Lugano 2014 criteria. Primary analysis population will be used for this endpoint. The distribution of progression free survival will be estimated using the method of Kaplan-Meier. Progression free survival will be compared between the 2 treatment arms using the log-rank test. The median progression free survival and corresponding 95% confidence intervals will be reported.

    Measured: From randomization to documentation of disease progression or death, assessed up to 5 years post-registration

  2. Event free survival

    Disease progression will be defined by Lugano 2014 criteria. Primary analysis population will be used for this endpoint. The distribution of event free survival will be estimated using the method of Kaplan-Meier. Event free survival will be compared between the 2 treatment arms using the log-rank test. The median event free survival and corresponding 95% confidence intervals will be reported.

    Measured: From randomization to documentation of disease progression, start of non-protocol lymphoma therapy, or death due to any cause, assessed up to 5 years post-registration

  3. Overall survival

    Primary analysis population will be used for this endpoint. The distribution of overall survival will be estimated using the method of Kaplan-Meier. Overall survival will be compared between the 2 treatment arms using the log-rank test. The median overall survival and corresponding 95% confidence intervals will be reported.

    Measured: From randomization to death due to any cause, assessed up to 5 years post-registration

  4. Duration of response

    Disease progression will be defined by Lugano 2014 criteria. Primary analysis population achieving response of CR or PR will be used for this endpoint. The distribution of duration of response will be estimated using the method of Kaplan-Meier. Duration of response will be compared between the 2 treatment arms using the log-rank test. The median duration of response and corresponding 95% confidence intervals will be reported.

    Measured: From first documentation of objective status of partial response (PR) or CR to documentation of disease progression, assessed up to 5 years post-registration

  5. Duration of complete response

    Disease progression will be defined by Lugano 2014 criteria. Primary analysis population achieving response of CR will be used for this endpoint. The distribution of duration of complete response will be estimated using the method of Kaplan-Meier. Duration of complete response will be compared between the 2 treatment arms using the log-rank test. The median duration of complete response and corresponding 95% confidence intervals will be reported.

    Measured: From first documentation of objective status of CR to documentation of disease progression, assessed up to 5 years post-registration

  6. Time to response

    Response will be defined by Lugano 2014 criteria. Primary analysis population achieving response of CR or PR will be used for this endpoint. The distribution of time to response will be estimated using descriptive statistics such as median and range. Time to response will be compared between the 2 treatment arms using the Wilcoxon-rank sum test.

    Measured: From randomization to the first documentation of objective status of PR or CR, assessed up to 5 years post-registration

  7. Objective response rate (ORR)

    Response will be defined by Lugano 2014 criteria. ORR is defined as the number of patients who experience objective response divided by the number of patients in primary analysis population. ORR will be compared between the 2 treatment arms. Confidence intervals for ORR will be calculated according to the approach of Clopper and Pearson. Overall response rate and the corresponding 95% confidence interval will be reported.

    Measured: From randomization up to one year

  8. Incidence of adverse events

    Primary analysis population will be used for adverse event analyses. The overall adverse event rates for grade 3 or higher adverse events will be reported. Further analysis of adverse event rates will be considered exploratory.

    Measured: Up to 1 year 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 posted2 Feb 2024
  2. Study start31 Jan 2024
  3. Primary completion31 Dec 2029 (estimated)
  4. Study completion31 Dec 2030 (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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06238648
Sponsor's protocol ID
ACCRU-LY-2201
Other IDs
NCI-2023-10170, ACCRU-LY-2201, P30CA015083
Status last verified
Sep 2024
First submitted
5 Jan 2024
Last updated
26 Sep 2024
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 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Diffuse Large B-Cell Lymphoma, Not Otherwise Specified and Primary Mediastinal Large B-Cell Lymphoma, run by Academic and Community Cancer Research United at 6 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 20 inclusion and 28 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 26 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective status of complete response (CR) (time frame: From randomization up to one year). 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 NCT06238648.

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 26 Sep 2024.

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