A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
NCT ID: NCT04442022
Last Updated: 2025-10-03
Study Results
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Basic Information
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RECRUITING
PHASE2/PHASE3
501 participants
INTERVENTIONAL
2020-09-03
2025-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
DOUBLE
Study Groups
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Phase 2: Selinexor 40 mg + R-GDP
Patients with RR DLBCL will receive combination therapy of selinexor 40 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally once weekly (QW) for each 28-day cycle until progressive disease (PD) or unacceptable toxicity.
Selinexor (combination therapy)
Dose: 40 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m\^2) on Day 1; Route of administration: intravenous (IV)
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Phase 2: Selinexor 60 mg + R-GDP
Patients with RR DLBCL will receive combination therapy of selinexor 60 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.
Selinexor (combination therapy)
Dose: 60 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Rituximab (combination therapy)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Phase 2: R-GDP
Patients with RR DLBCL will receive R-GDP on specified days (Days 1, 2, 3, 4, and 8) for each 21-day cycle for up to 6 cycles.
Rituximab (combination therapy)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg
Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.
Selinexor (combination therapy)
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
Rituximab (combination therapy)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo
Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.
Selinexor (combination therapy)
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
Rituximab (combination therapy)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Placebo matching for Selinexor (continuous therapy)
Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral
Phase 3: Placebo + R-GDP followed by Placebo
Patients with RR DLBCL will receive combination therapy of placebo matching for selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.
Placebo matching for Selinexor (combination therapy)
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
Rituximab (combination therapy)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Placebo matching for Selinexor (continuous therapy)
Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral
Interventions
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Selinexor (combination therapy)
Dose: 40 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Selinexor (combination therapy)
Dose: 60 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral
Selinexor (combination therapy)
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
Placebo matching for Selinexor (combination therapy)
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
Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m\^2) on Day 1; Route of administration: intravenous (IV)
Rituximab (combination therapy)
Dose: 375 mg/m\^2 on Day 1; Route of administration: IV
Gemcitabine (combination therapy)
Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV
Dexamethasone (combination therapy)
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
Cisplatin (combination therapy)
Dose: 75 mg/m\^2 on Day 1; Route of administration: IV
Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Placebo matching for Selinexor (continuous therapy)
Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral
Eligibility Criteria
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Inclusion Criteria
* Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen.
* Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy.
* Maintenance therapy will not be counted as a separate line of systemic therapy.
* Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy.
* Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (\>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi \>1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5.
* Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent \[%\] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician.
* Adequate bone marrow function at screening, defined as:
* Absolute neutrophil count (ANC) ≥1\*10\^9 per liter (/L).
* Platelet count ≥100\*10\^9/L (without platelet transfusion less than \[\<\] 14 days prior to Cycle 1 Day 1 \[C1D1\]).
* Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion \<14 days prior to C1D1).
* Circulating lymphocytes less than or equal to (≤) 50\*10\^9/L.
* Adequate liver and kidney function, defined as:
* Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5\*upper limit of normal (ULN), or ≤5\*ULN in cases with known lymphoma involvement in the liver.
* Serum total bilirubin ≤2\*ULN, or ≤5\*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver.
* Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
* An estimated life expectancy of \>3 months at Screening.
* Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study.
* Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment
* Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy).
* Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.
* Major surgery \<14 days of Cycle 1 Day 1.
* Hematopoietic stem cell transplantation/CAR-T therapy as follows:
* Autologous stem cell transplant (SCT) \<100 days or allogeneic-SCT \<180 days prior to C1D1
* Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis)
* CAR-T cell infusion \<90 days prior to Cycle 1
* Neuropathy Grade ≥2 (CTCAE, v.5.0).
* Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures.
* Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
* Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections:
* Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 International units (IU)/mL prior to first dose of study treatment.
* Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard.
* Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year.
* Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment.
* Breastfeeding or pregnant women.
* Inability or unwillingness to sign an informed consent form (ICF).
* In the opinion of the Investigator, patient who are significantly below their ideal body weight.
* Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment.
Exclusion Criteria
* Previous treatment with selinexor or other XPO1 inhibitors.
* Contraindication to any drug contained in the combination therapy regimen (SR-GDP).
* Known active central nervous system or meningeal involvement by DLBCL at time of Screening.
* Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) \<21 days prior to C1D1 (prednisone \<30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions).
18 Years
ALL
No
Sponsors
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Karyopharm Therapeutics Inc
INDUSTRY
Responsible Party
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Locations
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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
Investigative Clinical Research of Indiana, LLC
Indianapolis, Indiana, United States
Norton Cancer Institute, St. Matthews
Louisville, Kentucky, United States
Tulane Cancer Center
New Orleans, Louisiana, United States
University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, United States
Comprehensive Cancer Centers of Nevada - Town Center
Las Vegas, Nevada, United States
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, United States
Stony Brook
Stony Brook, New York, United States
Gabrail Cancer Center Research LLC
Canton, Ohio, United States
Texas Oncology - Medical City Dallas
Dallas, Texas, United States
Texas Oncology - Presbyterian Dallas Cancer Center
Dallas, Texas, United States
Texas Oncology - Sammons
Dallas, Texas, United States
Texas Oncology - Fort Worth
Fort Worth, Texas, United States
Texas Oncology - Plano East
Plano, Texas, 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
Providence Regional Cancer Partnership
Everett, Washington, United States
Kepler Universitaetskrankenhaus Med Campu III - Onkologie
Linz, Austria, Austria
University of Vienna, Medical Clinic I, Hematology
Vienna, Austria, Austria
Hospital Hietzing
Vienna, Austria, Austria
Jiangsu Province Hospital
Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School
Huangpu, Shanghai Municipality, China
Zhongshan Hospital Fudan University
Xuhui, Shanghai Municipality, China
Huaxi Hospital Sichuan University
Chengdu, Sichuan, China
The first affiliated Hospital, Zhejiang University
Hangzhou, Zhejiang, China
Assuta Ashdod Medical Center
Ashdod, , Israel
Soroka Medical Center
Beersheba, , Israel
Rambam health care campus (Department of Hematology & Bone Marrow Transplantation)
Haifa, , Israel
Wolfson Medical Center
Holon, , Israel
Hadassah Medical Center
Jerusalem, , Israel
Rabin Medical Center
Petah Tikva, , Israel
Assuta medical centers - Ramat Hachayal
Tel Aviv, , Israel
Sourasky Medical Center
Tel Aviv, , Israel
AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia
Ancona, Ancona, Italy
AOU Policlinico S.Orsola Malpighi di Bologna, University of Bologna
Bologna, Bologna, Italy
UOC Ematologia ad Indirizzo Oncologico, AORN "Sant'Anna e San Sebastiano"
Caserta, Caserta, Italy
National Cancer Institute
Naples, Napoli, Italy
AOU Maggiore della Carità SCDU Ematologia
Novara, Novara, Italy
DIP. Oncologia- Ematologia, UOSD Centro Diagnosie TerapiaDei Linfomi
Pescara, Pescara, Italy
Fondatione Policlinico Universitario A. Gemelli
Rome, Rome, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Palermo, Sicily, Italy
AOU City of Health and Science of Turin
Turin, Torino, Italy
Pratia MCM Krakow
Krakow, Lesser, Poland
Szpitale pomorskie gdynia dept of haematology
Gdynia, Pomeranian Voivodeship, Poland
Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wrocławiu
Wroclaw, Radeckiego, Poland
Pratia Onkologia Katowice
Katowice, Silesian Voivodeship, Poland
CM Pratia Poznań
Skorzewo, Wielkopolska, Poland
Institute of Hematology and Transfusion Medicine
Warsaw, , Poland
Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw, , Poland
Institut català d'oncologia-hospital germans trias i pujol
Badalona, Barcelona, Spain
Hospital Vall Hebron
Barcelona, Barcelona, Spain
Institut Catala D'oncolocia
Barcelona, Barcelona, Spain
Hospital Universitario La Paz
Madrid, Madrid, Spain
Hospital Virgen del Rocío
Seville, Seville, Spain
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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2020-000605-84
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
XPORT-DLBCL-030
Identifier Type: -
Identifier Source: org_study_id
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