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

NCT ID: NCT06977711

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-20
• Study Completion Date: 2026-07-31

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. To assess the safety and how well the participants tolerate the treatment

2. Assess the response of the tumor to treatment to estimate complete response

3. Assess the response of the tumor to treatment to estimate progression-free survival

Detailed Description

Exploratory analyses include cell free DNA (cfDNA). Each subject's disease will be biologically characterized at baseline.

Enrolled 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, in combination with loncastuximab 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.

All subjects will have PET-CT at four time points during the trial: 1) screening, 2) cycle 3 (after the 2 initial chemotherapy free cycles of therapy), 3) cycle 6 (after 3 cycles of loncastuximab, roflumilast and R-CHOP), and 4) at end of therapy (EOT) after completing a total of eight cycles of treatment planned for the trial (two chemotherapy free and six of chemoimmunotherapy). All subjects will have cfDNA monitoring at three time points during the trial: 1) cycle 1 day 1 (baseline), 2) cycle 3 day 1 (after the 2 initial chemotherapy free cycles of therapy), and 3) at end of therapy (EOT) after completing a total of eight cycles of treatment planned for the trial (two chemotherapy free and six of chemoimmunotherapy). Responses will be evaluated by PET-CT as per Lugano response criteria1 and correlated with cfDNA analysis. Cycles are 21 days long.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

Loncastuximab

Intervention Type: DRUG

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

Roflumilast

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Interventions

Loncastuximab

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

Intervention Type: DRUG

Roflumilast

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

Intervention Type: DRUG

Rituximab

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Vincristine

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men and women 18 years of age or older.

2. 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.

3. No prior systemic therapy for lymphoma.

4. Subject has provided informed consent.

5. Subject is willing and able to comply with clinic visits and procedure outlined in the study protocol.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

7. Life expectancy of ≥3 months.

8. Ann Arbor stage II-IV

9. National Comprehensive Cancer Network - International Prognostic Index (NCCN-IPI) risk score of ≥ 2

10. 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.

11. Left ventricular ejection fraction of at least 45% by either echocardiography or radionucleotide angiography.

12. Ability to swallow oral tablets without difficulty.

13. 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:

i) are not at least 50 years old and have no menses for 24 consecutive months; or ii) have not been rendered surgically sterile (having undergone hysterectomy and/or bilateral salpingo-oophorectomy).

Female subjects of reproductive potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (hCG) within 7 days of first day of drug dosing.

14. Meet the following clinical laboratory requirements:

• Creatinine clearance ≥30 ml/min by Cockcroft-Gault formula;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (unless indirect bilirubin is elevated due to Gilbert's syndrome or hemolysis);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤ 3 × ULN;
• Platelet count ≥ 50,000/µL, with or without transfusion support;
• Absolute Neutrophil Count (ANC) ≥ 1000/µL, with or without chronic granulocyte growth factor support;
• Hemoglobin ≥8 g/dL, with or without transfusion support.

Exclusion Criteria

1. Allergy or intolerance to roflumilast.

2. Allergy or intolerance to loncastuximab

3. Any active malignancy other than DLBCL

4. Current participation in another interventional clinical study

5. Prior allogeneic bone marrow transplant within 12 months of screening date.

6. Prior autologous stem cell transplant within 6 months of screening date.

7. Immunotherapy, chemotherapy, radiotherapy, or investigational therapy within 6 months prior to drug dosing.

8. Active central nervous system (CNS) involvement by lymphoma, including untreated symptomatic epidural disease.

9. Active uncontrolled infection.

10. Poorly controlled depressive symptoms and/ or currently under management for depression that is poorly controlled.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. Baseline serum troponin above the upper limit of normal.

17. Baseline serum brain natriuretic peptide (BNP )above the age-adjusted upper limit of normal.

18. Baseline amylase above the upper limit of normal.

19. Subjects known to be HIV-positive must not have multi-drug resistant HIV infection, cluster of differentiation 4 (CD4) counts < 150/µl or other concurrent AIDS-defining conditions. Serologic screening for HIV is required within the 6 months prior to study enrollment.

20. Subjects positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C-virus ribonucleic acid (HCV RNA), unless both AST and ALT≤1.25 x ULN and there is no known history of chronic active hepatitis.

Serologic screening for hepatitis B and C testing is required within the 6 months prior to study enrollment.

21. Subjects with moderate or severe liver impairment, as defined by a Child-Pugh class of B or C.

22. Women who are pregnant or breastfeeding.

23. Current use of any of the following medications: boceprevir, carbamazepine, ciprofloxacin, cobicistat, conivaptan, enzalutamide, fluvoxamine, itraconazole, ketoconazole, mitotane, phenytoin, posaconazole, rifampin, ritonavir, St. John's Wort, telaprevir, voriconazole, or zafirlukast.

24. Current use of non-nucleoside reverse transcriptase inhibitors (NNRTI) including efavirenz, rilpivirine, etravirine, delavirdine, nevirapine, and lersivirine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Adolfo Enrique Diaz Duque

Associate Professor/Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adolfo E Diaz Duque, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Ricardo Aguiar, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Locations

University Hospital System

San Antonio, Texas, United States

Site Status: RECRUITING

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

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Adolfo Diaz Duque, MD

Role: CONTACT

diazduque@uthscsa.edu

210-450-5904

Ricardo E Aguiar, MD

Role: CONTACT

aguiarr@uthscsa.edu

210-567-4860

Facility Contacts

Ricardo Aguiar, MD, PhD

Role: primary

aguiarr@uthscsa.edu

210-567-4860

Adolfo E Diaz Duque, MD, MSc

Role: backup

diazduque@uthscsa.edu

210-450-5904

Ricardo Adolfo Diaz Duque, MD, MSc

Role: primary

diazduque@uthscsa.edu

210-450-5904

Ricardo E Aguiar, MD, PhD

Role: backup

aguiarr@uthscsa.edu

210-567-4860

Other Identifiers

STUDY00001006

Identifier Type: OTHER

Identifier Source: secondary_id

CTMS# 24-0122

Identifier Type: -

Identifier Source: org_study_id