NCT06977711

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

Phase Ib Clinical Trial of Loncastuximab and Roflumilast Added to R-CHOP (Lo-RR-CHOP) for Treatment Naïve High-Risk Diffuse Large B-cell Lymphoma (DLBCL)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Sponsor: The University of Texas Health Science Center at San Antonio · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Loncastuximab	Intravenous (IV) administration 0.15 mg/kg day 1 cycles 1-2, and 0.075mg/kg day 1, cycles 3-5
DRUG	Roflumilast	Oral administration of 500mcg days 1-21, cycles 1-8
DRUG	Rituximab	IV administration of 375mg/m2 day 1, cycles 1-8
DRUG	Cyclophosphamide	IV administration of 750mg/m2 day 1, cycles 3-8
DRUG	Vincristine	IV administration 1.4mg/m2 (max 2mg) day 1, cycles 3-8
DRUG	Doxorubicin	IV administration 50mg/m2 day 1, cycles 3-8
DRUG	Prednisone	Oral administration 100mg/days 1-5, cycles 3-8

Timeline

• Start date: 2025-06-20
• Primary completion: 2026-04-15
• Completion: 2026-07-31
• First posted: 2025-05-18
• Last updated: 2025-08-05

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study