Loncastuximab and Roflumilast Added to R-CHOP (Lo-(Rituximab and Roflumilast) RR-CHOP) for Naïve High-Risk Diffuse Large B-cell Lymphoma (DLBCL)

NCT06977711 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CTMS# 24-0122STUDY00001006
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This study is developed by the investigator and is a, phase I, single arm, clinical trial that will enroll subjects with untreated diffuse large B-cell lymphoma (DLCBL) at high risk for poor outcome. The types of treatments given will be shared with participants. The aims are:

1. 1.To assess the safety and how well the participants tolerate the treatment
2. 2.Assess the response of the tumor to treatment to estimate complete response
3. 3.Assess the response of the tumor to treatment to estimate progression-free survival

Conditions

Diffuse Large B-cell Lymphoma

Keywords

Lymphoid neoplasms; Loncastuximab; Rituximab; Roflumilast; Lo-RR-CHOP; R-CHOP

Outcome Measures

Primary Outcomes (1)

• Estimation of number of adverse events

  Estimation of adverse events (AE) and serious adverse events (SAE), graded according to the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

  Baseline up to 8 cycles (up to 24 weeks)

Secondary Outcomes (2)

• Estimation of complete response

  Baseline up to 8 cycles (up to 24 weeks)

• Estimation of progression-free survival (PFS)

  Baseline up to 8 cycles (up to 24 weeks)

Study Arms (1)

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

EXPERIMENTAL

Eligible subjects will receive 2 cycles of chemotherapy free therapy composed of Loncastuximab 0.15 mg/kg, Rituximab 375 mg/m2, and Roflumilast 500 ug po daily; followed by 6 cycles of chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at standard of care (SOC) doses, and Roflumilast 500 ug po daily. Loncastuximab at a dose of 0.075 mg/kg will be added to other chemoimmunotherapy agents only for the first three (3) out of six (6) cycles

Drug: Loncastuximab; Drug: Roflumilast; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Prednisone

Interventions

Loncastuximab DRUG

Intravenous (IV) administration 0.15 mg/kg day 1 cycles 1-2, and 0.075mg/kg day 1, cycles 3-5

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Roflumilast DRUG

Oral administration of 500mcg days 1-21, cycles 1-8

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Rituximab DRUG

IV administration of 375mg/m2 day 1, cycles 1-8

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Cyclophosphamide DRUG

IV administration of 750mg/m2 day 1, cycles 3-8

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Vincristine DRUG

IV administration 1.4mg/m2 (max 2mg) day 1, cycles 3-8

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Doxorubicin DRUG

IV administration 50mg/m2 day 1, cycles 3-8

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Prednisone DRUG

Oral administration 100mg/days 1-5, cycles 3-8

Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)

Eligibility Criteria

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

You may qualify if:

• Men and women 18 years of age or older.
• Pathologically proven diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS).
• \- Patients with Diffuse large B-cell lymphoma/ high grade B-cell lymphoma with MYC (myelocytomatosis oncogene) and BCL2 (B-cell lymphoma 2) rearrangements are allowed.
• No prior systemic therapy for lymphoma.
• Subject has provided informed consent.
• Subject is willing and able to comply with clinic visits and procedure outlined in the study protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy of ≥3 months.
• Ann Arbor stage II-IV
• National Comprehensive Cancer Network - International Prognostic Index (NCCN-IPI) risk score of ≥ 2
• Measurable disease, meaning at least 1 lymph node or other lymphomatous lesion with a long axis of ≥1.5 cm by CT imaging, and at least one FDG-avid lesion by FDG-PET scan.
• Left ventricular ejection fraction of at least 45% by either echocardiography or radionucleotide angiography.
• Ability to swallow oral tablets without difficulty.
• All subjects with preserved reproductive potential must agree to practice abstinence or employ contraceptive measures for the duration of treatment and for 10 months (if female) or 7 months (if male) following final dosing. All male subjects are considered to have reproductive potential.
• Female subjects of reproductive potential are those who:

You may not qualify if:

• Allergy or intolerance to roflumilast.
• Allergy or intolerance to loncastuximab
• Any active malignancy other than DLBCL
• Current participation in another interventional clinical study
• Prior allogeneic bone marrow transplant within 12 months of screening date.
• Prior autologous stem cell transplant within 6 months of screening date.
• Immunotherapy, chemotherapy, radiotherapy, or investigational therapy within 6 months prior to drug dosing.
• Active central nervous system (CNS) involvement by lymphoma, including untreated symptomatic epidural disease.
• Active uncontrolled infection.
• Poorly controlled depressive symptoms and/ or currently under management for depression that is poorly controlled.
• Significant disease or medical conditions, as assessed by the Investigator and Sponsor, that would substantially increase the risk benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV.
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which subjects are not on active anti-cancer therapies and have had no evidence of active malignancy for at least 1 year.
• History of major surgery within 3 weeks or minor surgery within 1 week of roflumilast administration. Major surgery includes, for example, any open or laparoscopic entry into a body cavity, or operative repair of fracture; minor surgery includes, for example, open surgical biopsy of palpable/superficial lymph node, or placement of vascular access device.
• Other medical or psychiatric illnesses or organ dysfunction, which in the opinion of the investigator, would either compromise the subject's safety or interfere with the evaluation of the safety of the study agent.
• Corrected QT interval (QTc) prolongation (defined as a QTc \>450 ms for males and \>470 ms for females -Fridericia's correction-) or other clinically significant ECG abnormalities as assessed by the investigator.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (2)

University Hospital System

San Antonio, Texas, 78228, United States

RECRUITING

University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

loncastuximab tesirine; Roflumilast; Rituximab; Cyclophosphamide; Vincristine; Doxorubicin; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Adolfo E Diaz Duque, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

• Ricardo Aguiar, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adolfo Diaz Duque, MD

CONTACT

210-450-5904; diazduque@uthscsa.edu

Ricardo E Aguiar, MD

CONTACT

210-567-4860; aguiarr@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor/Clinical

Model Details: Phase I, single arm, open label clinical trial that

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: May 18, 2025
• Study Start: June 20, 2025
• Primary Completion: April 15, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At study conclusion after data is analyzed and published in a peer review journal.

Locations

US (2)