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
• 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.
• 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:
⁃ 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.
⁃ 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.