Parsaclisib Plus the Standard Drug Therapy in Patients With Newly Diagnosed, High Risk Diffuse Large B-cell Lymphoma

PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of parsaclisib in combination with R-CHOP in newly diagnosed diffuse large B-cell lymphoma (DLBCL). (Phase I) II. To assess the complete metabolic response rate by positron emission tomography (PET) (PET complete response \[CR\]) of combining parsaclisib and R-CHOP in patients with newly diagnosed DLBCL. (Dose Expansion) III. To assess significant toxicities of parsaclisib in combination with polatuzumab vedotin (pola) and R-CHP in newly diagnosed DLBCL. (Pola Safety Lead-in) SECONDARY OBJECTIVES: I. To describe the toxicities associated with parsaclisib in combination with R-CHOP. (Phase I) II. To assess the objective response rate (ORR) of parsaclisib in combination with R-CHOP. (Dose Expansion) III. To assess the duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) in patients treated with parsaclisib in combination with R-CHOP. (Dose Expansion) IV. To further describe the toxicities associated with parsaclisib in combination with R-CHOP. (Dose Expansion) V. To describe the toxicities associated with parsaclisib in combination with polatuzumab vedotin and R-CHP. (Pola Safety Lead-in) VI. To assess the PET CR rate and ORR of parsaclisib in combination with polatuzumab vedotin and R-CHP. (Pola Safety Lead-in) VII. To assess the duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) in patients treated with parsaclisib in combination with polatuzumab vedotin and R-CHP. (Pola Safety Lead-in) OUTLINE: This is a phase I, dose-escalation study of parsaclisib, and safety lead-in of pola. ARM I (PHASE I AND DOSE EXPANSION): Patients receive parsaclisib orally (PO) once daily (QD) on days 1-10 or 1-14, rituximab intravenously (IV) or biosimilar substitute, cyclophosphamide IV over 30 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV over 15 minutes on day 1. Patients also receive prednisone PO on days 1-5 and pegfilgrastim subcutaneously (SC) or biosimilar substitute on day 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. ARM II (PHASE I AND POLA SAFETY LEAD-IN): Patients receive parsaclisib PO once daily QD on days 1-10 or 1-14, polatuzumab vedotin IV over 90 minutes, rituximab IV or biosimilar substitute, cyclophosphamide IV over 30 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV over 15 minutes on day 1. Patients also receive prednisone PO on days 1-5 and pegfilgrastim SC or biosimilar substitute on day 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months during year 1 and every 4 months during year 2. Patients who experience disease progression before the end of year 2 are followed up every 6 months until 5 years after registration.