Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma

Eligibility Criteria

• * Participants must satisfy the following criteria to be enrolled in the study:
• 1. Is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• 2. Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated, a-BCL according to 2016 WHO classification.
• 3. Participant has International Prognostic Index (IPI) score 0-5 in Part 1 and IPI 2-5 in Part 2. For the CELMoD and polatuzumab-R-CHP cohort, the subject must also have IPI score 0 to 5 in Part 2A and IPI 2 to 5 in Part 2B.
• 4. Participants must have measurable disease defined by at least one FDG-avid lesion for FDG-avid subtype and one bi-dimensionally measurable (\> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification (Cheson, 2014).
• 5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• 6. Participants must have the following laboratory values:
• 1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L in case of documented bone marrow involvement (\> 50% or tumor cells), without growth factor support for 7 days (14 days if peg-G-CSF)
• 2. Hemoglobin (Hb) ≥ 8 g/dL
• 3. Platelets (PLT) ≥ 75 x 109/L or ≥ 50 x 109/L in case of documented bone marrow involvement (\>50% or tumor cells), without transfusion for 7 days
• 4. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamate pyruvic transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN). In the case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
• 5. Serum total bilirubin ≤ 2.0 mg/dL except in cases of Gilbert's syndrome, then ≤ 5.0 mg/dl. Subjects receiving polatuzumab vedotin must have serum total bilirubin \< 1.5 × ULN (26 μmol/L) (corresponding to mild degree as per National Cancer Institute Organ Dysfunction Working Group \[NCI ODWG\] criteria) except in cases of Gilbert's syndrome, then ≤ 3.0 mg/dl (51 μmol/L).
• 6. Estimated serum creatinine clearance (CrCl) of ≥ 50 mL/min using the modification of diet in renal disease (MDRD) formula.
• 7. All participants must:
• 1. Have an understanding that the study drug could have a potential teratogenic risk.
• 2. Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 or CC-99282 Pregnancy Prevention Plan for Participants in Clinical trials.
• 8. Females of childbearing potential (FCBP) must:
• 9. Male participants must:
• 1. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study.
• * The presence of any of the following will exclude a participant from enrollment:
• 1. Any significant medical condition, active infection (including SARS-CoV-2 suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
• 2. Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
• 3. Any other subtype of lymphoma.
• 4. Documented or suspected CNS involvement by lymphoma.
• 5. Persistent diarrhea or malabsorption ≥ Grade 2 (NCI CTCAE v5.0), despite medical management.
• 6. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
• 7. Subjects with a history of progressive multifocal leukoencephalopathy.
• 8. Chronic systemic immunosuppressive therapy or corticosteroids
• 9. Impaired cardiac function or clinically significant cardiac disease, including any of the following:
• 10. Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery.
• 11. Any condition causing inability to swallow tablets.
• 12. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)
• 13. Known chronic active hepatitis B (hepatitis B virus surface antigen \[HBsAg\] positive and/or hepatitis B core antibody \[anti-HBc\] positive with viral DNA positive) or C (positive serology requiring treatment and/or with evidence of liver damage) infection
• 14. History of other malignancy, unless being free of the disease for ≥ 3 years; exceptions to the ≥ 3-year time limit include history of the following:
• 1. Localized nonmelanoma skin cancer
• 2. Carcinoma in situ of the cervix
• 3. Carcinoma in situ of the breast
• 4. Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node Metastasis \[TNM\] staging system) or prostate cancer that has been treated with curative intent.
• 15. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or polatuzumab vedotin.
• 16. Known hypersensitivity to any component of CHOP/CHP regimen.
• 17. Known allergy to thalidomide, pomalidomide, or lenalidomide.