Loncastuximab Tesirine and Rituximab as Bridging Therapy Before Standard-of-care CAR-T Therapy in Patients With Large B-cell Lymphoma (CORAL)

NCT06788964 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCI184585
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed or Refractory Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• 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.

  1 month

• 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

  1 month

• Severity of cytopenias post CAR-T (as defined by the NIH CTCAE, version 5.0) D30 (+/- 7 days).

  To evaluate toxicities post CAR-T

  1 month

• Rate of infections D30 (+/- 7 days).

  To evaluate toxicities post CAR-T

  1 month

Secondary Outcomes (9)

• 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)

  5 years

• ORR defined as the proportion of subjects achieving a confirmed PR or CR at D30 (+/- 7 days) post CAR-T per Lugano 2014 criteria1.

  1 month

• Best response rate per Lugano 2014 criteria following CAR-T (based on imaging up until D90 post CAR-T)

  3 months

• ORR defined as the proportion of subjects achieving a confirmed PR or CR post lonca-R (pre-CAR-T)

  5 years

• Level of disease control (measured as percentage) with lonca-R as evaluated by CT measurements and metabolic tumor volume on PET pre and post Lonca-R

  5 years

Study Arms (1)

Treatment: All Patients

EXPERIMENTAL

The study will investigate the effectiveness of Loncastuximab tesirine and Rituximab (Lonca-R) prior to standard of care CAR-T cell therapy.

Drug: Loncastuximab Tesirine; Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab is administered intravenously for 1-6 cycles (every 21 days) prior to standard of care CAR-T cell therapy.

Also known as: RITUXAN

Treatment: All Patients

Loncastuximab Tesirine DRUG

Patients will receive Loncastuximab Tesirine intravenously for 1-6 cycles (every 21 days) prior to standard of care CAR-T cell therapy.

Also known as: ZYNLONTA

Treatment: All Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) disease following at least one multi-agent systemic treatment regimen.
• Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if the tumor is not fluorodeoxyglucose (FDG)-avid on screening PET-CT.
• ECOG Performance Status ≤ 2.
• Time between prior anticancer therapy and first dose of lonca-R as below
• Autologous hematopoietic cell transplantation - At least 30 days
• Allogeneic hematopoietic cell transplantation - At least 60 days
• Cytotoxic chemotherapy - At least 21 days
• Non-cytotoxic chemotherapy (e.g., small molecule inhibitor) - At least 14 days
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1000/mm3

You may not qualify if:

• 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.
• Subjects with chronic liver disease with hepatic impairment Child-Pugh class C
• Pregnant or lactating or intending to become pregnant during the study
• Active graft-versus-host disease
• Post-transplantation lymphoproliferative disorders
• Active autoimmune disease which, in the opinion of the investigator, may negatively impact subject safety or interfere with study participation.
• The diagnosis of another malignancy which, in the opinion of the investigator, is likely to negatively impact subject safety or interfere with study participation.
• Subjects with known CNS involvement.
• Significant medical diseases or conditions including those requiring substantial changes in concomitant medications, as assessed by the investigator, that would substantially increase the risk-to-benefit ratio of participating in the study. This includes, but is not limited to the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• Myocardial infarction (MI) within 6 months before the first dose.

Sponsors & Collaborators

• University of Utah: lead
• ADC Therapeutics S.A.: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

loncastuximab tesirine; Rituximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Narendranath Epperla, MD, MS, FACP

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Kingsford

CONTACT

801-585-0115; rachel.kingsford@hci.utah.edu

Narendranath Epperla, MD, MS, FACP

CONTACT

801-585-0255; naren.epperla@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2025
• First Posted: January 23, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2030
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)