- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05796271
Clinical Trial of Roflumilast Added to Standard Chemoimmunotherapy
Clinical Trial of Roflumilast Added to Standard Chemoimmunotherapy for High-risk Diffuse Large B-cell Lymphoma (CTMS# 22-0016)
Study Overview
Study Type
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78229
- Mays Cancer Center, UT Health San Antonio
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women 18 years of age or older.
- Pathologically proven diffuse large B-cell lymphoma.
- No prior systemic therapy for lymphoma.
- Patient has provided informed consent.
- Patient 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
- 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 4 weeks following final dosing. All male subjects are considered to have reproductive potential. Female subjects of reproductive potential are those who: 1) are not at least 50 years old and have no menses for 24 consecutive months; or 2) 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);
- AST and ALT≤ 3 × ULN;
- Platelet count ≥ 50,000/μL, with or without transfusion support;
- ANC ≥ 1000/μL, with or without chronic granulocyte growth factor support;
- Hemoglobin ≥8 g/dL, with or without transfusion support.
Exclusion Criteria:
2. Any active malignancy other than DLBCL 3. High grade B Cell Lymphoma with rearrangements of MYC and BCL2, MYC and BCL6, and /or MYC and BCL2/BCL6 ("double-hit" or "triple-hit" 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 illness 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 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, 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: R-Chop and Roflumilast
All subjects will receive R-CHOP therapy at standard doses according to the standard preparation and infusion procedures of each investigational site, which is to be repeated every 21 days (+/- 3 days) for a total of 6 cycles.
All subjects will receive a fixed oral dose of one 500 microgram (μg) tablet of roflumilast per day with or without food for all 21 days of each cycle, which will amount to a total of 126 doses.
Subjects will be asked to keep a drug diary to record the days and times when Roflumilast is taken.
The first dose will be given on the day of the first R-CHOP treatment.
|
All subjects will receive R-CHOP therapy at standard doses according to the standard preparation and infusion procedures of each investigational site, which is to be repeated every 21 days (+/- 3 days) for a total of 6 cycles.
All subjects will receive a fixed oral dose of one 500 microgram (μg) tablet of roflumilast per day with or without food for all 21 days of each cycle, which will amount to a total of 126 doses.
Subjects will be asked to keep a drug diary to record the days and times when Roflumilast is taken.
The first dose will be given on the day of the first R-CHOP treatment.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anti-tumor efficacy: progression-free survival (PFS)
Time Frame: Measured every 3 weeks for 21 day cycles for the duration of study treatment, from Baseline to approximately one year
|
To assess the change in anti-tumor efficacy of Roflumilast in combination with R-CHOP in subjects with previously untreated high-risk DLBCL who are appropriate for treatment by estimates of progression-free survival (PFS).
|
Measured every 3 weeks for 21 day cycles for the duration of study treatment, from Baseline to approximately one year
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTMS# 22-0016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lymphoma, B-Cell
-
Iksuda Therapeutics Ltd.RecruitingFollicular Lymphoma | B-cell Lymphoma | Mantle Cell Lymphoma | Diffuse Large B Cell Lymphoma | B-cell Non-Hodgkin LymphomaAustralia, Canada, United States
-
Nathan DenlingerBristol-Myers SquibbRecruitingB-Cell Non-Hodgkin Lymphoma-Recurrent | Diffuse Large B-Cell Lymphoma-Recurrent | Follicular Lymphoma-Recurrent | High Grade B-Cell Lymphoma-Recurrent | Primary Mediastinal Large B-Cell Lymphoma-Recurrent | Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent and other conditionsUnited States
-
AstraZenecaRecruitingFollicular Lymphoma | Diffuse Large B Cell Lymphoma | High-grade B-cell Lymphoma | B-cell Non Hodgkin LymphomaKorea, Republic of, United States, Japan, Australia, Taiwan
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
-
Massachusetts General HospitalVarian Medical SystemsNot yet recruitingLymphoma, B-Cell | Follicular Lymphoma | Mantle Cell Lymphoma | Diffuse Large B Cell Lymphoma | Refractory Lymphoma | High-grade B-cell Lymphoma | Relapsed Cancer | Mediastinal Large B-cell LymphomaUnited States
-
University of ChicagoMerck Sharp & Dohme LLCRecruitingLymphoma | Lymphoma, B-Cell | B Cell Lymphoma | Diffuse Large B Cell Lymphoma | High-grade B-cell LymphomaUnited States
-
Curocell Inc.RecruitingHigh-grade B-cell Lymphoma | Diffuse Large B-cell Lymphoma (DLBCL) | Primary Mediastinal Large B-Cell Lymphoma (PMBCL) | Transformed Follicular Lymphoma (TFL) | Refractory Large B-cell Lymphoma | Relapsed Large B-cell LymphomaKorea, Republic of
-
University Hospital Southampton NHS Foundation...Hoffmann-La RocheTerminatedDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited Kingdom
-
Qian WenbinNot yet recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaChina
-
The Lymphoma Academic Research OrganisationActive, not recruitingRefractory Indolent Adult Non-Hodgkin Lymphoma | Refractory Mantle Cell Lymphoma | Diffuse Large B-Cell Lymphoma Refractory | Refractory Transformed B-cell Non-Hodgkin Lymphoma | Refractory Primary Mediastinal Large B-Cell Cell LymphomaFrance
Clinical Trials on R-Chop and Roflumilast
-
Nanjing Yoko Biomedical Co., Ltd.RecruitingDiffuse Large B-Cell Lymphoma, Unspecified SiteChina
-
Fondazione Italiana Linfomi ONLUSUnknown
-
CTI BioPharmaCompletedDiffuse Large-Cell LymphomaUnited States, Germany, Canada, Italy, France
-
Dana-Farber Cancer InstituteGenentech, Inc.RecruitingRichter SyndromeUnited States
-
Ruijin HospitalUnknownDiffuse Large B-cell Lymphoma | Follicular Lymphoma Grade 3BChina
-
Shandong Cancer Hospital and InstituteThe First Affiliated Hospital of Nanchang UniversityRecruitingThe First Affiliated Hospital of Nanchang UniversityChina
-
University Health Network, TorontoActive, not recruiting
-
University of Wisconsin, MadisonCompletedLymphoma, Large B-Cell, DiffuseUnited States
-
Johnson & Johnson Pharmaceutical Research & Development...Completed
-
Nordic Lymphoma GroupRoche Pharma AGRecruitingDiffuse Large B Cell Lymphoma | DLBCLFinland, Norway, Denmark, Italy, Sweden, Australia, New Zealand