Epcoritamab Compared to Observation for Treating B-cell Lymphoma Patients Not in Complete Remission After CD19-directed CAR-T Therapy
Multicenter, Randomized Phase II Study of Epcoritamab for Patients With Aggressive B-Cell Lymphomas Achieving a Partial Response After CD19-Directed CAR-T Therapy
3 other identifiers
interventional
120
1 country
6
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2024
Longer than P75 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 5, 2024
CompletedStudy Start
First participant enrolled
January 31, 2024
CompletedFirst Posted
Study publicly available on registry
February 2, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2030
September 26, 2024
September 1, 2024
5.9 years
January 5, 2024
September 24, 2024
Conditions
Outcome Measures
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.
From randomization up to one year
Secondary Outcomes (8)
Progression free survival
From randomization to documentation of disease progression or death, assessed up to 5 years post-registration
Event free survival
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
Overall survival
From randomization to death due to any cause, assessed up to 5 years post-registration
Duration of response
From first documentation of objective status of partial response (PR) or CR to documentation of disease progression, assessed up to 5 years post-registration
Duration of complete response
From first documentation of objective status of CR to documentation of disease progression, assessed up to 5 years post-registration
- +3 more secondary outcomes
Study Arms (2)
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.
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.
Interventions
Undergo collection of blood samples
Undergo PET/CT and/or CT
Given SC
Undergo MRI
Undergo observation
Undergo PET/CT
Eligibility Criteria
You may qualify if:
- 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:
- +5 more criteria
You may not qualify if:
- 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.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Grzegorz S Nowakowski
Academic and Community Cancer Research United
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 5, 2024
First Posted
February 2, 2024
Study Start
January 31, 2024
Primary Completion (Estimated)
December 31, 2029
Study Completion (Estimated)
December 31, 2030
Last Updated
September 26, 2024
Record last verified: 2024-09