Trial Title:
Epcoritamab Compared to Observation for Treating B-cell Lymphoma Patients Not in Complete Remission After CD19-directed CAR-T Therapy
NCT ID:
NCT06238648
Condition:
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
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Antibodies, Bispecific
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy
Arm group label:
Arm A (epcoritamab)
Arm group label:
Arm B (observation)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Arm A (epcoritamab)
Arm group label:
Arm B (observation)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo PET/CT and/or CT
Arm group label:
Arm A (epcoritamab)
Arm group label:
Arm B (observation)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Epcoritamab
Description:
Given SC
Arm group label:
Arm A (epcoritamab)
Other name:
Anti-CD20/CD3 Bispecific Antibody GEN3013
Other name:
DuoBody-CD3xCD20
Other name:
Epcoritamab-bysp
Other name:
Epkinly
Other name:
GEN 3013
Other name:
GEN-3013
Other name:
GEN3013
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm A (epcoritamab)
Arm group label:
Arm B (observation)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Other
Intervention name:
Patient Observation
Description:
Undergo observation
Arm group label:
Arm B (observation)
Other name:
Active Surveillance
Other name:
deferred therapy
Other name:
expectant management
Other name:
Observation
Other name:
Watchful Waiting
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Arm A (epcoritamab)
Arm group label:
Arm B (observation)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
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.
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.
Criteria for eligibility:
Criteria:
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:
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
ACCRU Operations
Phone:
507-538-7448
Email:
ACCRU@mayo.edu
Investigator:
Last name:
Grzegorz S. Nowakowski
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Dilan A. Patel
Email:
dpatel1@wustl.edu
Investigator:
Last name:
Dilan A. Patel
Email:
Principal Investigator
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Lori Leslie
Email:
Lori.Leslie@hmhn.org
Investigator:
Last name:
Lori Leslie
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Miguel-Angel Perales
Email:
peralesm@mskcc.org
Investigator:
Last name:
Miguel-Angel Perales
Email:
Principal Investigator
Facility:
Name:
UNC Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Natalie S. Grover
Email:
natalie_grover@med.unc.edu
Investigator:
Last name:
Natalie S. Grover
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Allison Bock
Email:
allison.bock@hci.utah.edu
Investigator:
Last name:
Allison Bock
Email:
Principal Investigator
Start date:
January 31, 2024
Completion date:
December 31, 2030
Lead sponsor:
Agency:
Academic and Community Cancer Research United
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Academic and Community Cancer Research United
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06238648
