The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram \[mg\] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
501
Dose: 40 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Dose: 60 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Dose: Selected dose of selinexor (from Phase 2) on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Dose: Placebo matching for selected dose of selinexor (from Phase 2) on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Dose: 375 milligram per meter square (mg/m\^2) on Day 1; Route of administration: intravenous (IV)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dose: 40 mg (20 mg if patient is more than 70 years old) on Days 1, 2, 3, and 4; Route of administration: oral or IV
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral
Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
Chandler, Arizona, United States
Arizona Oncology Associates
Tucson, Arizona, United States
The Oncology Institute (TOI) Clinical Research
Cerritos, California, United States
Norton Cancer Institute, St. Matthews
Louisville, Kentucky, United States
University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014
Time frame: From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
Phase 3: Progression-free Survival (PFS): Based on Lugano Criteria 2014
Time frame: From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Phase 2: Progression-free Survival: Based on Lugano Criteria 2014
Time frame: From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Phase 2: Overall Survival (OS)
Time frame: From date of initial randomization until death (maximum of 5 years from randomization)
Phase 3: Overall Response Rate: Based on Lugano Criteria 2014
Time frame: From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
Phase 3: Overall Survival
Time frame: From date of initial randomization until death (maximum of 5 years from randomization)
Phase 2: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Lugano Criteria 2014
Time frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 2: Overall Response Rate at the End of Combination Therapy: Based on Modified Lugano Criteria
Time frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 2: Duration of Response (DOR): Based on Lugano Criteria 2014
Time frame: From time of first response until disease progression or death (maximum of 5 years from randomization)
Phase 2: Number of Patients with Adverse Events (AEs)
Time frame: Up to 30 days after last dose of study drug (maximum of 5 years from randomization)
Phase 3: Overall Response Rate at the End of Combination Therapy: Based on Lugano Criteria 2014
Time frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 3: Overall Response Rate at the End of Combination Therapy: Based on Modified Lugano Criteria
Time frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 3: Duration of Response: Based on Lugano Criteria 2014
Time frame: From time of first response until disease progression or death (maximum of 5 years from randomization)
Phase 3: Progression-free Survival: Based on Modified Lugano Criteria
Time frame: From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Phase 3: Number of Patients with Adverse Events
Time frame: Up to 30 days after last dose of study drug (maximum of 5 years from randomization)
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Stony Brook
Stony Brook, New York, United States
Texas Oncology - Tyler
Tyler, Texas, United States
The University of Texas Health Science Center at Tyler DBA UT Health East Texas HOPE Cancer Center
Tyler, Texas, United States
Jiangsu Province Hospital
Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
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