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Lay Description

This study is an investigator-initiated, phase I, single arm, open label clinical trial that will enroll subjects with untreated diffuse large B-cell lymphoma (DLCBL) at high risk for poor outcome, defined as an NCCN-IPI score of 2 or higher.

Category

  • Cancers and Other Neoplasms
  • Hematological Malignancy
IRB Number
STUDY00001006
NCT Number
NCT06977711

Eligibility

Eligible Ages
18-99
Eligible Genders
Male and female
Accepts Healthy Volunteers
No

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 and BCL2 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. 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 12 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: 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.

  1. 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.

        15. No use of strong CYP3A4 inducers or inhibitors within 7 days prior                              to Cycle 1 Day 1.

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. Subjects with rapidly progressive disease, bulky disease with clinical instability, or end-organ dysfunction due to lymphoma requiring immediate cytoreductive therapy.
  6. Prior allogeneic bone marrow transplant within 12 months of screening date.
  7. Prior autologous stem cell transplant within 6 months of screening date.
  8. Immunotherapy, chemotherapy, radiotherapy, or investigational therapy within 6 months prior to drug dosing.
  9. Active central nervous system (CNS) involvement by lymphoma, including untreated symptomatic epidural disease.
  10. Active uncontrolled infection.
  11. Poorly controlled depressive symptoms and/ or currently under management for depression that is poorly controlled.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. Baseline serum troponin above the upper limit of normal.
  18. Baseline serum BNP above the age-adjusted upper limit of normal.
  19. Baseline amylase above the upper limit of normal.
  20. 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.
  21. 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.
  22. Subjects with moderate or severe liver impairment, as defined by a Child-Pugh class of B or C.
  23. Women who are pregnant or breastfeeding.
  24. Current use of strong CYP3A4 inducers, inhibitors, or dual CYP3A4/CYP1A2 inhibitors 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, due to potential interaction with study drugs. A ≥7-day washout period is required before initiating study treatment.
  25. Current use of non-nucleoside reverse transcriptase inhibitors (NNRTI) including efavirenz, rilpivirine, etravirine, delavirdine, nevirapine, and lersivirine.

Study Design

Arm Groups

Study Contact

Frances Crawford
210-450-5037
crawfordf1@uthscsa.edu

Myrna Montenegro
210-450-5954
montenegro@uthscsa.edu

Kathleen Rodriguez
210-450-1365
rodriguezk3@uthscsa.edu

Benjamin Schleif
210-450-1366
schleifb@uthscsa.edu

Morgan Seekatz
210-450-1133
seekatz@uthscsa.edu

Adolfo Diaz Duque
210-450-5904
diazduque@uthscsa.edu

Principal Investigator
Adolfo Diaz Duque