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Diffuse Large B-cell LymphomaPhase 1NCT06977711

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

A Phase 1 study testing Loncastuximab, Roflumilast and Rituximab in people with Diffuse Large B-cell Lymphoma, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
Loncastuximab, Roflumilast and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesUnited States
Study dates
20 Jun 2025to 1 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 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.
  • 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.

Who cannot join

  • 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.
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  • 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.
  • Baseline serum troponin above the upper limit of normal.
  • Baseline serum brain natriuretic peptide (BNP )above the age-adjusted upper limit of normal.
  • Baseline amylase above the upper limit of normal.
  • 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.
  • 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.
  • Subjects with moderate or severe liver impairment, as defined by a Child-Pugh class of B or C.
  • Women who are pregnant or breastfeeding.
  • 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.
  • Current use of non-nucleoside reverse transcriptase inhibitors (NNRTI) including efavirenz, rilpivirine, etravirine, delavirdine, nevirapine, and lersivirine.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Adolfo Diaz Duque, MD contact

210-450-5904

diazduque@uthscsa.edu

Ricardo E Aguiar, MD contact

210-567-4860

aguiarr@uthscsa.edu

United States2 sites, 2 recruiting

  • University Hospital System

    San Antonio, Texas, 78228

    Ricardo Aguiar, MD, PhD, 210-567-4860, aguiarr@uthscsa.edu

    Adolfo E Diaz Duque, MD, MSc, 210-450-5904, diazduque@uthscsa.edu

    Recruiting

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

    San Antonio, Texas, 78229

    Ricardo Adolfo Diaz Duque, MD, MSc, 210-450-5904, diazduque@uthscsa.edu

    Ricardo E Aguiar, MD, PhD, 210-567-4860, aguiarr@uthscsa.edu

    Recruiting

Other trials in United States

About this study

Official title: 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)

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
Read the 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.

Being tested
Loncastuximab, Roflumilast, Rituximab, Cyclophosphamide, Vincristine
Keywords
Lymphoid neoplasms, Loncastuximab, Rituximab, Roflumilast, Lo-RR-CHOP, R-CHOP
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LoncastuximabDrug

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

  • RoflumilastDrug

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

  • RituximabDrug

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

  • CyclophosphamideDrug

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

  • VincristineDrug

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

  • DoxorubicinDrug

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

  • PrednisoneDrug

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

Study groups in NCT06977711
Study groupRoleWhat they receive
Untreated High Risk DLBCL (Diffuse Large B-cell Lymphoma)ExperimentalEligible 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
Receives: Drug: Loncastuximab; Drug: Roflumilast; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline up to 8 cycles (up to 24 weeks)

Secondary outcomes (2)

  1. Estimation of complete response

    Estimation of complete response (CR) as defined by complete normalization of fluorodeoxyglucose positron emission tomography (FDG-PET) uptake (Deauville score of 1 to 3) of all target lesions

    Measured: Baseline up to 8 cycles (up to 24 weeks)

  2. Estimation of progression-free survival (PFS)

    Estimation of progression-free survival (PFS) defined as the time from the date of registration until the date of disease progression or death as a result of any cause.

    Measured: Baseline up to 8 cycles (up to 24 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2025
  2. Study start20 Jun 2025
  3. Primary completion15 Oct 2026 (estimated)
  4. Study completion1 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase I, single arm, open label clinical trial that
Masking
None (open label)
Enrolment
10 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06977711
Sponsor's protocol ID
CTMS# 24-0122
Other IDs
STUDY00001006
Status last verified
Jun 2026
First submitted
9 May 2025
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: A description of study results will be provided at the end of the study. It will include a summary of overall entry status of all enrolled patients, and an account of all identified protocol violations. Patients who do not qualify for analysis, who die during the study, or who withdraw from the study before receiving treatment will be reported.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Loncastuximab, Roflumilast and Rituximab in people with Diffuse Large B-cell Lymphoma, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Adolfo Diaz Duque, MD (210-450-5904, diazduque@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Estimation of number of adverse events (time frame: Baseline up to 8 cycles (up to 24 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06977711.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.

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