The purpose of this clinical trial is to learn if the study treatment Loncastuximab tesirine and Rituximab is safe and efficient before standard of care chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory large B-cell lymphoma.
Subject aged ≥ 18 years.
Intended to receive commercial CD19-directed CAR-T cell therapy (axi-cel and liso-cel).
Need for bridging therapy as deemed clinically necessary by the treating physician.
Relapsed or refractory DLBCL, tFL or PMBCL as defined by the 2016 World Health Organization classification (including patients with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma (HGBL), not otherwise specified, and HGBL with MYC and BCL2 and/or BCL6 rearrangements.
Previous treatment with any anti-CD19 therapy including lonca or prior CD19 CAR T-cell therapy
Subjects receiving investigational CAR-T products
Major surgery within 4 weeks prior to starting study therapy.
History of bleeding diathesis (e.g., von Willebrand's disease), hemophilia, or active bleeding.
Single group
Loncastuximab Tesirine
DrugPatients will receive Loncastuximab Tesirine intravenously for 1-6 cycles (every 21 days) prior to standard of care CAR-T cell therapy.
Rituximab
DrugRituximab is administered intravenously for 1-6 cycles (every 21 days) prior to standard of care CAR-T cell therapy.
The complete response (CR) rate at D30 post CAR-T(+/- 7 days) post CAR-T administration per Lugano 2014 criteria.
To evaluate the efficacy of SOC CAR T-cell therapy in patients with R/R large B-cell lymphoma following bridging with lonca-R.
Duration of cytopenias post CAR-T (as defined by the NIH CTCAE, version 5.0) D30 post CAR-T (+/- 7 days).
To evaluate toxicities post CAR-T
Severity of cytopenias post CAR-T (as defined by the NIH CTCAE, version 5.0) D30 (+/- 7 days).
To evaluate toxicities post CAR-T
Rate of infections D30 (+/- 7 days).
To evaluate toxicities post CAR-T
CD19 expression as measured by flow cytometry and IHC on biopsies obtained pre- and post-lonca-R (optional) and post-CAR-T (optional but strongly recommended)
To determine whether CD19 expression is reduced in patients who receive bridging with lonca-R prior to CAR-T.
ORR defined as the proportion of subjects achieving a confirmed PR or CR at D30 (+/- 7 days) post CAR-T per Lugano 2014 criteria1.
To evaluate the level of disease control provided by bridging lonca-R
Best response rate per Lugano 2014 criteria following CAR-T (based on imaging up until D90 post CAR-T)
To evaluate the level of disease control provided by bridging lonca-R
ORR defined as the proportion of subjects achieving a confirmed PR or CR post lonca-R (pre-CAR-T)
To evaluate the level of disease control provided by bridging lonca-R
Click on the lead sponsor to view all of their trials.
University of Utah
Lead sponsor
ADC Therapeutics S.A.
Collaborator
