High-grade B-cell Lymphoma, Lymphoma, Non-Hodgkin, Refractory Diffuse Large B-cell Lymphoma, Relapsed Diffuse Large B Cell Lymphoma, Transformed Indolent Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
Conditions
Brief summary
This study investigates the feasibility and efficacy of epcoritamab treatment before CAR T cells. This study also investigates if, when patients have residual lymphoma after CAR T cells, epcoritamab can help to effectively treat that lymphoma.
Interventions
DRUGEpcoritamab
* C1D1: fixed priming dose of 0.16 mg subcutaneous injection * C1D8: fixed intermediate dose of 0.8 mg subcutaneous injection * C1D15 onward: fixed full dose of 48 mg subcutaneous injection
Sponsors
Abramson Cancer Center at Penn Medicine
Genmab
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Subject must be able and willing to provide informed consent. In the case where the patient is incapacitated or not otherwise capable, a legally authorized representative (or decision maker when there is not an advanced directive in place) must be willing to provide informed consent on behalf of the patient. * Able to comply with the study protocol, in the investigator's judgment * ECOG PS of 0 - 2 * Pathology report confirming eligible diagnosis * Documented CD20+ tumor cells on most recent biopsy * Patients will have failed to respond to frontline standard of care therapy containing an anthracycline and anti-CD20 antibody * Patients will be eligible and consent to be treated with a "commercially available" anti-CD19, 4-1BB, CD3zeta CAR-T cell therapy or anti-CD19, CD28, CD3zeta CAR T cell therapy (for example, tisagenlecleucel, lisocabtagene maraleucel, or axicabtagene maraleucel) * Patients must have a PET/CT scan (preferred), diagnostic CT scan, or MRI with at least one bi-dimensionally measurable lesion (≥ 1.5 cm for nodal lesions or ≥ 1cm for extra-nodal lesions in largest dimension by low-dose computerized tomography \[CT\] scan with FDG-uptake ≥ liver) * Adequate laboratory studies * Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator * Ability and willingness to take proper contraceptive precautions
Exclusion criteria
* Inability or unwillingness of the patient or legally authorized representative (or decision-maker when there is not an advanced directive in place) to provide informed consent. * Prior solid organ transplantation * Primary central nervous system (CNS) lymphoma or active secondary CNS involvement by lymphoma at screening as confirmed by magnetic resonance imaging (MRI)/computed tomography (CT) scan (brain) or, if clinically indicated, by lumbar puncture. * History of autoimmune disease or other diseases resulting in permanent immunosuppression or requiring chronic immunosuppressive therapy (see
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of CAR T cell infusion among subjects who receive epcoritamab and undergo leukapheresis | Start of epcoritamab to CAR T-cell infusion | Whether participants receive CAR T-cell infusion (yes/no) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of AEs, SAEs from epcoritamab until CAR T cell infusion | Day 1 of epcoritamab until CAR T cell infusion | Assessment of toxicity via incidence and severity of AEs and SAEs via CTCAE v5 |
| Overall Response Rate after 2 cycles of Epcoritamab | Day 1 of epcoritamab to completion of 2 cycles of epcoritamab | Percentage of subjects who receive epcoritamab and have a CR or PR by Lugano 2014 criteria prior to CAR T-cells |
| Incidence and severity of AEs, SAEs after CAR T cell infusion through day 28 visit after CAR T-cell infusion | CAR T cell infusion through day 28 visit after CAR T-cells | Assessment of toxicity via incidence and severity of AEs and SAEs via CTCAE v5 |
| Day 28 visit response rates post CAR T cell infusion | Day 28 visit after CAR T cell infusion | Overall response rate as well as complete response rate after CAR T-cells |
| Progression-free survival, duration of response, and overall survival for those subjects achieving complete response at Day 28 visit post CAR T cell infusion | CAR T cell infusion until last follow-up or death | Duration of response from day 28 visit after CAR T-cells, progression-free survival and overall survival from CAR T-cell infusion |
| Incidence and severity of AEs, SAEs from day 28 visit after CAR T-cell infusion until epcoritamab discontinuation | Day 28 visit after CAR T-cell infusion until epcoritamab discontinuation up to 12 cycles of epcoritamab | Assessment of toxicity via incidence and severity of AEs and SAEs via CTCAE v5 |
| Responses at 3 and 6 months after CAR T-cell infusion for subjects who receive epcoritamab after CAR T-cells | 3 and 6 months after CAR T-cell infusion | Best overall response rate, overall response rate, and complete response rate at 3 and 6 months after CAR T cell infusion for subjects who receive epcoritamab after CAR T-cells |
| Duration of response, progression-free survival and overall survival from time of CAR T-cell infusion for subjects who receive post CAR T-cell epcoritamab infusions | From CAR T-cell infusion until date of last follow-up or date of death due to any cause, whichever comes first, assessed up to 5 years from last dose of epcoritamab | Duration of response from first response after CAR T-cell infusion, progression-free survival and overall survival from CAR T-cell infusion |
Countries
United States
Contacts
CONTACTBrittany Koch
CONTACTKaitlin Kennard
PRINCIPAL_INVESTIGATORElise Chong, MD
Abramson Cancer Center at the University of Pennsylvania
Outcome results
None listed