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RecruitingNCT06238648Updated Sep 26, 2024

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

A Phase 2 interventional study of Biopsy and Biospecimen Collection in Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Primary Mediastinal Large B-Cell Lymphoma and Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma, sponsored by Academic and Community Cancer Research United. Recruiting at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-26.

Sponsored by Academic and Community Cancer Research United · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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. 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:

I. 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:

I. 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.

V. 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:

I. 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.

02

Conditions studied

  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal Large B-Cell Lymphoma
  • Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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)
  • 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

Exclusion criteria

Exclusion Criteria:

  • 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)
  • 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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Arm A (epcoritamab)

    Patients 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.

    Procedure: Biopsy · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Biological: Epcoritamab · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography

  • Active comparator
    Arm B (observation)

    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.

    Procedure: Biopsy · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Other: Patient Observation · Procedure: Positron Emission Tomography

Interventions

  • ProcedureBiopsy

    Undergo biopsy

    Also known as: BIOPSY_TYPE, Bx

  • ProcedureBiospecimen Collection

    Undergo collection of blood samples

    Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

  • ProcedureComputed Tomography

    Undergo PET/CT and/or CT

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

  • BiologicalEpcoritamab

    Given SC

    Also known as: Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, Epkinly, GEN 3013, GEN-3013, GEN3013

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

    Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • OtherPatient Observation

    Undergo observation

    Also known as: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

  • ProcedurePositron Emission Tomography

    Undergo PET/CT

    Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

05

What researchers measure

Primary outcomes

  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.

    Time frame: From randomization up to one year

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: Up to 1 year post-treatment

06

Study locations

1 of 6 sites recruiting
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
    • ACCRU Operations · Contact · ACCRU@mayo.edu · 507-538-7448
    • Grzegorz S. Nowakowski · Principal investigator
    Not yet recruiting
  • Siteman Cancer Center at Washington University
    Saint Louis, Missouri 63110, United States
    • Dilan A. Patel · Contact · dpatel1@wustl.edu
    • Dilan A. Patel · Principal investigator
    Not yet recruiting
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
    Not yet recruiting
  • Memorial Sloan Kettering Cancer Center
    New York, New York 10065, United States
    • Miguel-Angel Perales · Contact · peralesm@mskcc.org
    • Miguel-Angel Perales · Principal investigator
    Not yet recruiting
  • UNC Lineberger Comprehensive Cancer Center
    Chapel Hill, North Carolina 27599, United States
    Not yet recruiting
  • Huntsman Cancer Institute/University of Utah
    Salt Lake City, Utah 84112, United States
    Recruiting
07

Registry details

Key details

Study ID
NCT06238648
Lead sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Feb 2, 2024
Start date
Jan 31, 2024
Primary completion
Dec 31, 2029 (estimated)
Completion
Dec 31, 2030 (estimated)
Last update
Sep 26, 2024

Study contacts

Grzegorz S Nowakowski
principal investigator · Academic and Community Cancer Research United

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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