This is a Phase 1/2, multicenter, open-label study to evaluate the efficacy, and safety of various combinations with selinexor in participants with RR DLBCL. The study will be conducted in two phases: Phase 1 and 2. The Phase 1 of the study will be a standard 3 + 3 dose escalation to determine the maximal tolerated dose (MTD), recommended Phase 2 dose (RP2D) for each treatment arm, and assess the dose limiting toxicities (DLTs). The Phase 2 of the study will be a dose expansion study to assess the efficacy and safety of for RP2D selected at the end of Phase 1 of the study for each treatment arm.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Dose: 375 mg/m\^2
Dose: 90 mg/m\^2
University of Arizona
Tucson, Arizona, United States
California Cancer Associates for Research and Excellence
Encinitas, California, United States
Phase 1: Maximum Tolerated Dose (MTD)
Time frame: Within the first cycle (maximum 28 days) of treatment
Phase 1: Recommended Phase 2 Dose (RP2D)
Time frame: Up to 6 cycles (up to 6 months) of treatment
Phase 2: Overall Response Rate (ORR) per the Lugano Classification 2014
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a complete response (CR) or partial response (PR) (up to 6 months)
Phase 1: Overall Response Rate per the Lugano Classification 2014
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a complete response (CR) or partial response (PR) (up to 6 months)
Phase 1: Disease Control Rate (DCR) per Lugano Classification 2014
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a CR or PR or stable disease (SD) (up to 6 months)
Phase 1: Duration of Response (DOR) per Lugano Classification 2014
Time frame: Time from the first response of PR or CR until disease progression (up to 12 months)
Phase 1: Overall Response Rate (ORR) per the Modified Lugano Classification
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a CR or PR (up to 6 months)
Phase 1: Number of Participants With Adverse Events (AEs) by Occurrence, Nature, and Severity
Time frame: From start of study drug administration up to 30 days after last dose of study treatment (up to 24 months)
Phase 2: Overall Response Rate per the Modified Lugano Classification
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Dose: 1.8 mg/kg
Dose: 420, 560 mg
Dose: 20, 25 mg
Dose: 12 mg/kg
Dose: 200, 400, 600, 800 mg
Dose: 1000 mg/m\^2
Dose: 100 mg/m\^2
UC San Diego Moores Cancer Center
La Jolla, California, United States
University of California Irvine
Orange, California, United States
US Oncology - Rocky Mountain Cancer Center
Aurora, Colorado, United States
Loyola University Medical Center
Maywood, Illinois, United States
Mission Cancer + Blood
Des Moines, Iowa, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
...and 8 more locations
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a complete response (CR) or partial response (PR) (up to 6 months)
Phase 2: Disease Control Rate (DCR) per Lugano Classification 2014
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a CR or PR or stable disease (SD) (up to 6 months)
Phase 2: Duration of Response (DOR) per Lugano Classification 2014
Time frame: Time from the first response of PR or CR until disease progression or death (up to 12 months)
Phase 2: Number of Participants With AEs by Occurrence, Nature, and Severity
Time frame: From start of study drug administration up to 30 days after last dose of study treatment (up to 24 months)