ClinicalTrials.gg
RecruitingNCT06977711Updated Sep 29, 2026

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 interventional study of Loncastuximab and Roflumilast in Diffuse Large B-cell Lymphoma, sponsored by The University of Texas Health Science Center at San Antonio. Recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by The University of Texas Health Science Center at San Antonio · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Started Jun 2025; still recruiting 1 year 4 months later.

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Phase
Phase 1
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-14

Among 1,131 studies in Lymphoma, Large B-Cell, Diffuse with a site in United States — 126 open to participants now, 218 under way, 18 of them phase 3. Lymphoma, Large B-Cell, Diffuse · United States.

Planned enrollment
800th of 963
10 · median 37
Started
2025
with 27 others
Phase 1
395 of 1,131
42 open now
Primary completion
2026-10
later than 55 of 217 live
Registered
1,096th of 1,131
by date

Among the 1,131 studies in Lymphoma, Large B-Cell, Diffuse with a site in United States, this one is the 800th largest by planned enrollment of the 963 interventional ones that give a count, is one of 28 that started in 2025, is one of 395 in phase 1, reaches primary completion later than 55 of the 217 other live ones, and was the 1,096th registered.

Lymphoma, Large B-Cell, Diffuse

1,870 studies on the registry are indexed under Lymphoma, Large B-Cell, Diffuse; 357 are open to participants now.

Browse Lymphoma, Large B-Cell, Diffuse studies →

Open to participants now

126 of the 1,131 studies in Lymphoma, Large B-Cell, Diffuse with a site in United States are open now. Recruiting first, the newest first:

121 more — sign in →

All 126 open studies →

A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →

Who these studies take

Of the 266 Lymphoma, Large B-Cell, Diffuse studies recruiting now, 177 (67%) set no upper age limit and 51 (19%) stop at 75 or younger; 25 take children under 18; 7 take healthy volunteers.

This study: 18 Years and older · all sexes · no healthy volunteers.

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02

Study 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
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.

03

Conditions studied

  • Diffuse Large B-cell Lymphoma

Keywords

  • Lymphoid neoplasms
  • Loncastuximab
  • Rituximab
  • Roflumilast
  • Lo-RR-CHOP
  • R-CHOP
04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Men and women 18 years of age or older.
  2. 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 .
  5. Subject is willing and able to comply with clinic visits and procedure outlined in the study protocol.
  6. (ECOG) performance status of 0-2.
  7. of ≥3 months.
  8. Ann Arbor stage II-IV
  9. National Comprehensive Cancer Network - International Prognostic Index (NCCN-IPI) risk score of ≥ 2
  10. , 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. of at least 45% by either echocardiography or radionucleotide angiography.
  12. Ability to swallow oral tablets without difficulty.
  13. All subjects with preserved must agree to practice abstinence or employ 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:

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

Exclusion criteria

Exclusion Criteria:

  1. Allergy or intolerance to roflumilast.
  2. Allergy or intolerance to loncastuximab
  3. Any active other than DLBCL
  4. Current participation in another interventional clinical study
  5. Prior 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 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 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 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. interval (QTc) prolongation (defined as a QTc >450 ms for males and >470 ms for females -Fridericia's correction-) or other abnormalities as assessed by the investigator.
  16. Baseline serum troponin above the .
  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 -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 surface antigen (HBsAg) or -virus ribonucleic acid (HCV RNA), unless both 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 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.
Terms in these criteria, in plain language(27)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (estimated)

Study arms

  • Experimental
    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

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

Interventions

  • DrugLoncastuximab

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

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

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

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

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

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

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

06

What researchers measure

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.

    Time frame: Baseline up to 8 cycles (up to 24 weeks)

Secondary outcomes

  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

    Time frame: 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.

    Time frame: Baseline up to 8 cycles (up to 24 weeks)

07

Study locations

2 of 2 sites recruiting
  • 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
08

References and documents

Individual participant data

Plan to share: 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.

Supporting information: Study protocol, Statistical analysis plan

Time frame: At study conclusion after data is analyzed and published in a peer review journal.

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Jun 2025 (actual). Primary completion is estimated for Oct 2026, 15 months after the start.

Of 112 non-industry phase 1 interventional studies under Lymphoma, Large B-Cell, Diffuse, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 39 and three quarters within 86. This study's planned 15 months is below that.

Counting every sponsor, half of 196 studies reached it within 55 months; a quarter within 36 and three quarters within 82.

How these figures are worked out, and which studies are left out of them.

Registered
May 9, 2025
First posted
May 18, 2025
StartActual
Jun 20, 2025
Primary completionEst.
Oct 15, 2026
CompletionEst.
Apr 1, 2027
Last update
Sep 29, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 29, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06977711
Responsible party
Adolfo Enrique Diaz Duque (Associate Professor/Clinical, The University of Texas Health Science Center at San Antonio) — Principal investigator
First posted
May 18, 2025
Start date
Jun 20, 2025
Primary completion
Oct 15, 2026 (estimated)
Completion
Apr 1, 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Adolfo Diaz Duque, MD
Contact
diazduque@uthscsa.edu
210-450-5904
Ricardo E Aguiar, MD
Contact
aguiarr@uthscsa.edu
210-567-4860
Adolfo E Diaz Duque, MD
principal investigator · The University of Texas Health Science Center at San Antonio
Ricardo Aguiar, MD
principal investigator · The University of Texas Health Science Center at San Antonio

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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