A Combination of Rituximab and CC-99282 as Front-line Therapy for Older Frail Patients With Diffuse Large B-cells Non-Hodgkin Lymphoma Evaluated With a Simplified Geriatric Assessment (sGA): a Phase II Study of the Fondazione Italiana Linfomi (FIL)

Inclusion Criteria20

• Able to provide written informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study- specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
• Histologically documented diagnosis of DLBCL as defined in the 5th edition of the World Health Organization (WHO) classification (2022)
• Previously untreated
• Frail patients defined as follows (Appendix A-D): Age ≥ 80 years: activity of daily living (ADL) \< 6 residual functions and/or Instrumental activity of daily living (IADL) \< 8 residual functions and/or cumulative illness rating scale (CIRS) \> 5 comorbidities of grade 2 and/or one or more comorbidities of grade 3-4
• Patient not eligible to anthracycline-based chemotherapy
• Ann Arbor Stage I - IV (Appendix E)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 3 (Appendix F)
• At least one site of measurable nodal disease at baseline \[≥ 1.5 cm\] in the longest transverse diameter as determined by CT scan
• Adequate hematological counts defined as follows:
• WBC \> 2.5 x 109/L with ANC \> 1.0 x 109/L unless due to bone marrow involvement by lymphoma
• Platelet count ≥ 75 x 109/L unless due to bone marrow involvement by lymphoma
• Hemoglobin ≥ 10 g/dL unless anemia related to active lymphoma
• Adequate renal function defined as creatinine clearance ≥ 30 mL/min (Appendix G). The same CrCl cutoff applies in case of documented renal involvement by lymphoma
• Adequate hepatic function per local laboratory reference range, unless secondary to lymphoma, as follows:
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.0 x ULN
• Bilirubin ≤ 2 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, i.e. mild and chronic hemolysis)
• Subject must be able to adhere to the study visit schedule and other protocol requirements
• Subject must be able to swallow capsules or tablets
• Life expectancy ≥ 3 months
• Male subjects must practice complete abstinence when this is in line with the usual lifestyle (periodic abstinence is not permitted) or agree to use specified contraceptive methods (barrier contraception: condom) during sexual contact with a female of childbearing potential while participating in the study, for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy. Furthermore, they do not have to donate sperm during the study and for at least 28 days after receiving the last dose of study drug. If applicable, male subjects must receive study specific Pregnancy Prevention Plan (PPP).