Loncastuximab Tesirine and Rituximab Following Stereotactic Radiosurgery in Patients With Central Nervous System Lymphomas (SOLAR)

NCT06607549 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI181535
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to learn if drugs loncastuximab tesirine and rituximab (lonca-R) after stereotactic radiosurgery are safe and effective for treatment of central nervous system lymphomas.

Conditions

Central Nervous System Lymphoma

Outcome Measures

Primary Outcomes (1)

• A safe and tolerable dose of lonca-R following SRS in patients with CNS lymphoma who have relapsed disease or are untreated and not candidates for HDMTX-based therapy.

  Maximum Tolerated Dose (MTD): MTD is defined as the highest dose under consideration that has an estimated DLT probability below 25% based upon the Bayesian optimal interval design. The MTD will be decided based on the BOIN decision rules set for phase 1a portion of the study.

  5 years

Secondary Outcomes (3)

• To assess best overall response rate (ORR) following lonca-R

  6 months

• To assess best complete response (CR) rate following lonca-R.

  6 months

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment.

  5 years

Study Arms (1)

Treatment: All Patients

EXPERIMENTAL

This study has two main goals: Goal 1: The study will investigate the safety and tolerability of loncastuximab tesirine and rituximab (lonca-R). Goal 2: The study will determine the maximum tolerated dose of lonca-R.

Drug: Loncastuximab tesirine and rituximab (Lonca-R)

Interventions

Loncastuximab tesirine and rituximab (Lonca-R) DRUG

Patients will receive stereotactic radiosurgery (SRS) followed by a brain MRI approx. 3 weeks after SRS. This will be followed by loncastuximab tesirine and rituximab administered intravenously for a total of 6 cycles (every 21 days).

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:

• Participant aged ≥ 18 years
• ECOG Performance Status ≤ 3
• Histologically confirmed primary CNS lymphoma or secondary diffuse large B-cell lymphoma (DLBCL) with CNS involvement with either:
• Relapsed or refractory disease with at least 1 prior therapy OR
• Ineligible for high-dose methotrexate-based therapy as determined by the treating physician, including previously untreated patients. Examples of medical conditions for which a patient could be considered ineligible for high-dose methotrexate include but not limited to renal impairment, liver disease, heart failure.
• Note: For patients with a history of histologically documented systemic DLBCL with CNS relapse, a biopsy of the CNS lesion is recommended but not required.
• Must be a candidate for SRS. Lesion size must be \< 6 cm and the number of lesions must be \< 10.
• Must have evaluable disease. This includes radiographic evidence of parenchymal disease or parenchymal disease and disease detected in the CSF.
• Patients with vitreous or retinal involvement alone are not eligible.
• Patients with leptomeningeal disease or spinal cord disease are not eligible.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count ≥ 1000 cells/mm3 (1.00 x 109/L) independent of G-CSF support (i.e. no G-CSF within the past 3 days) unless there is documented bone marrow involvement.
• Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) independent of transfusion support (i.e. no transfusion within the past 3 days) unless there is documented bone marrow involvement.
• Hemoglobin ≥ 8 g/dL (≥ 80 g/L) independent of transfusion support (i.e. no transfusion within the past 3 days) unless there is documented bone marrow involvement.

You may not qualify if:

• Concurrent use of other approved or investigational antineoplastic agents (with the exception of corticosteroids).
• History of intracranial hemorrhage or clinically significant stroke within 6 months prior to enrollment
• History of prior radiation to the CNS.
• Significant medical diseases or conditions, 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, acute myocardial infarction in the past 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, severely immunocompromised state, and congestive heart failure, New York Heart Association Class III-IV.
• Known bleeding diathesis (e.g., von Willebrand's disease), hemophilia, or active bleeding.
• Known Human immunodeficiency virus (HIV) infection.
• Prior exposure to loncastuximab tesirine
• Chemotherapy or targeted small molecule therapy (or other therapy for CNS lymphoma) within 3 weeks prior to the first day of study treatment (or 5 half-lives (whichever is shorter), or 2 weeks prior to the first day of study treatment for monoclonal antibodies.
• The patient must have recovered to baseline or ≤ grade 1 from prior toxicities of therapy with the exception of alopecia and myelosuppression provided lab criteria met. Recovery to ≤ grade 2 neuropathy is permitted.
• Cellular therapy within 8 weeks.
• Presence of clinically significant pericardial or pleural effusions, or third space fluid accumulations (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).
• Congenital long QT syndrome or a corrected QT measure (QTc) interval of \>480 ms at screening (unless secondary to pacemaker or bundle branch block).
• Known history of hypersensitivity to CD19 antibody and/or, components of study medication.
• All subjects must be screened for hepatitis B and C. Patients with evidence of active hepatitis B infection, based on positive surface antigen or Hepatitis B DNA PCR are excluded. Patients who are Hepatitis B core antibody positive must take prophylaxis with entecavir or equivalent and be willing to undergo monthly Hepatitis B DNA PCR testing. Subjects with active Hep C patients may be enrolled if other parameters precluding hepatic impairment are met and they are not undergoing active therapy for hepatitis C.
• Active systemic bacterial, viral, fungal, or other infection requiring systemic treatment at time of screening.

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

Interventions

loncastuximab tesirine; Rituximab

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

  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

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: September 23, 2024
• Study Start: March 18, 2025
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)