Study of Selinexor in Combination With Backbone Treatments or Novel Therapies In Participants With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)
NCT ID: NCT04607772
Last Updated: 2025-10-03
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE1/PHASE2
INTERVENTIONAL
2020-11-18
2025-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP
NCT02741388
A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
NCT04442022
Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
NCT02227251
Selinexor Combined With R-GDP Regimen for TP53-altered R/R DLBCL
NCT06062641
Efficacy and Safety Study of Selinexor in Relapsed or Refractory Peripheral T-cell Lymphoma or Cutaneous T-cell Lymphoma
NCT02314247
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Arm A: Selinexor with Bendamustine and Rituximab (S-BR))
Participants will receive a dose of 40 or 60 or 80 milligrams (mg) of selinexor oral tablets on Days 1, 3, and 8 for Cycle 1 to 6 (each cycle consists of 21 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an intravenous (IV) dose of bendamustine 90 milligram per square meter (mg/m\^2) on Days 1 and 2 and IV dose of rituximab 375 mg/m\^2 on Day 1 during primary treatment for Cycle 1 to 6.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Bendamustine
Dose: 90 mg/m\^2
Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR)
Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 3, and 8 for Cycle 1 to 6 (each cycle consists of 21 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of polatuzumab vedotin 1.8 milligram per kilogram (mg/kg) and IV dose of rituximab 375 mg/m\^2 on Day 1 during primary treatment for Cycle 1 to 6.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Polatuzumab Vedotin
Dose: 1.8 mg/kg
Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR)
Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 3, and 8 for Cycle 1 to 6 (each cycle consists of 21 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of polatuzumab vedotin 1.8 mg/kg and IV dose of rituximab 375 mg/m\^2 on Day 1, and IV dose of bendamustine 90 mg/m\^2 on Days 1 and 2 during primary treatment for Cycle 1 to 6.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Bendamustine
Dose: 90 mg/m\^2
Polatuzumab Vedotin
Dose: 1.8 mg/kg
Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx)
Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1 and 3 for Cycle 1 to 6 (each cycle consists of 14 days) during primary treatment and 60 mg on Days 1, 8, 15, and 22 during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of rituximab 375 mg/m\^2, IV dose of gemcitabine 1000 mg/m\^2, and Oxaliplatin IV dose of 100 mg/m\^2 on Day 1 during primary treatment for Cycle 1 to 6.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Gemcitabine
Dose: 1000 mg/m\^2
Oxaliplatin
Dose: 100 mg/m\^2
Arm E: Selinexor with Ibrutinib and Rituximab (S-IR)
Participants will receive a dose of 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 8, and 15 for Cycle 1 to 6 during primary treatment and 40 mg (dose level 1) then 60 mg (dose level 2-4) during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of rituximab 375 mg/m\^2 on Day 1, and ibrutinib oral dose of 420 or 560 mg once daily on Day 1 to 28 during primary treatment for Cycle 1 to 6. Participants will also receive ibrutinib oral dose of 420 mg once daily at all dose levels during continuous treatment.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Ibrutinib
Dose: 420, 560 mg
Arm F: Selinexor with Lenalidomide and Rituximab (S-LR)
Participants will receive a dose of 40 or 60 mg of selinexor oral tablets on Days 1, 8, and 15 for Cycle 1 to 6 during primary treatment and 40 mg (dose level 1) then 60 mg (dose level 2) during continuous treatment (each cycle consists of 28 days). Participants will also receive an IV dose of rituximab 375 mg/m\^2 on Day 1, and lenalidomide oral dose of 20 mg once daily on Days 1 to 21 during primary treatment for Cycle 1 to 6. Participants will also receive lenalidomide oral dose of 20 mg on Days 1 to 21 at all dose levels during the continuous treatment.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Lenalidomide
Dose: 20, 25 mg
Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT)
Participants will receive a dose of 40 or 60 mg of selinexor oral tablets on Days 1, 8, and 15 for Cycle 1 to 12 during primary treatment and 40 (dose level 1) then 60 mg (dose level 2) during continuous treatment (each cycle consists of 28 days). During the primary treatment, participants will also receive lenalidomide oral dose of 25 mg once daily on Days 1 to 21, and tafasitamab IV dose of 12 mg/kg on Days 1, 8, 15, and 22 for Cycle 1 to 3 and Days 1 and 15 for Cycle 4 to 12. Participants will also receive an IV dose of tafasitamab 12 mg/kg on Days 1 and 15 for all dose levels during the continuous treatment.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Lenalidomide
Dose: 20, 25 mg
Tafasitamab
Dose: 12 mg/kg
Arm H: Selinexor with Venetoclax (S-V)
Participants will receive 40 or 60 or 80 mg of selinexor oral tablets on Days 1, 8 and 15 for Cycle 1 to 6 of primary treatment and 40 mg (dose level 1) then 60 mg (dose level 2-5) during continuous treatment (28 days per cycle). Participants who received 40 and 60 mg of selinexor during primary treatment will also receive oral dose of venetoclax 200 mg on Days 1 to 7 then 400 mg on Days 8 to 28 for Cycle 1; 400 mg daily for Cycle 2 to 6. Participants who received 60 and 80 mg of selinexor during primary treatment will also receive venetoclax 400 mg orally on Days 1 to 7 then 600 mg on Days 8 to 28 for Cycle 1; 600 mg daily for Cycle 2 to 6. Participants who received 80 mg selinexor during primary treatment will also receive venetoclax 400 mg orally on Days 1 to 7, then 600 mg from Days 8 to 14, then 800 mg from Day 15 to 28 for Cycle 1; 800 mg daily for Cycle 2 to 6. Participants during continuous treatment will also receive venetoclax 400 mg orally daily.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Venetoclax
Dose: 200, 400, 600, 800 mg
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Selinexor
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
Rituximab
Dose: 375 mg/m\^2
Bendamustine
Dose: 90 mg/m\^2
Polatuzumab Vedotin
Dose: 1.8 mg/kg
Ibrutinib
Dose: 420, 560 mg
Lenalidomide
Dose: 20, 25 mg
Tafasitamab
Dose: 12 mg/kg
Venetoclax
Dose: 200, 400, 600, 800 mg
Gemcitabine
Dose: 1000 mg/m\^2
Oxaliplatin
Dose: 100 mg/m\^2
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Have pathologically confirmed relapsed/refractory (RR) DLBCL, not otherwise specified (NOS).
3. Participants with High Grade B-cell Lymphoma (HGBL) are allowed in Phase 2 only.
4. Prior lines of systemic therapy for the treatment of DLBCL:
* For Arms A, B, C, E, F, G, H: Participants must have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL.
* For Arm D (S-R-GemOx) participants must have received at least 1 but not more than 2 lines of systemic therapy.
5. Positron emission tomography (PET) positive measurable disease per the Lugano Classification 2014, having at least 1 node with longest diameter (LDi) greater than (\>) 1.5 centimetres (cm) or 1 extranodal lesion with LDi \>1 cm.
6. Adequate bone marrow function at Screening.
7. Circulating lymphocytes less than or equal to (≤) 50 \* 109/L.
8. Adequate liver and kidney function.
9. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
10. An estimated life expectancy of \>6 months at Screening.
11. Participants with primary refractory disease defined as no response or relapse within 6 months after ending first-line treatment will be allowed on study (up to 20 percentage \[%\] of enrolled participants in each Phase).
12. Male participants, and female participants of childbearing potential must agree to use highly effective methods of contraception during the duration of the study and will continue following the last dose of study treatment for the longest duration stated on the label of each of the given drugs (depending on each arm).
13. Female participants of childbearing potential must have a negative serum pregnancy test at Screening. Female participants of childbearing potential in the S-LR arm and the S-LT arm must have 2 negative pregnancy tests before Lenalidomide treatment (Non-Childbearing potential: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy).
14. Participants with active hepatitis B Virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 international units per milliliter (IU/mL); participants with untreated hepatitis C Virus (HCV) are eligible if viral load is negative per institutional standard; participants with human immunodeficiency virus (HIV) are eligible if cluster of differentiation 4 (CD4+) T-cell counts ≥350 cells per microliter (cells/μL), viral load is negative and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
Exclusion Criteria
2. Previous treatment with selinexor or other XPO1 inhibitors.
3. Contraindication to any drug contained in the different treatment arms.
4. 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 Cycle 1 Day 1 (C1D1). Low dose steroids \<30 mg prednisone (or equivalent) and palliative radiotherapy are permitted.
5. Received strong cytochrome P450 3A (CYP3A) inhibitors ≤7 days prior to Day 1 dosing or strong CYP3A inducers ≤14 days prior to Day 1 dosing.
6. Any AE, by Cycle 1 Day 1 (C1D1), which has not recovered to Grade ≤1 (CTCAE, v. 5.0), or returned to baseline, related to the previous DLBCL therapy, except alopecia.
7. Major surgery \<14 days of C1D1.
8. Autologous stem cell transplant (SCT) \<100 days or allogeneic SCT \<180 days prior to C1D1 or active graft-versus-host disease after allogeneic SCT (or cannot discontinue graft versus host disease \[GVHD\] treatment or prophylaxis).
9. Prior chimeric antigen receptor T cell (CAR-T cell) infusion at any time (Phase 1 only); prior CAR-T cell infusion ≤120 days prior to C1D1 (Phase 2 only).
10. Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety, or able to comply with the study procedures.
11. 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).
12. Inability to swallow tablets, malabsorption syndrome, or any other GI disease or dysfunction that could interfere with absorption of study treatment.
13. Breastfeeding women or pregnant women.
14. Inability or unwillingness to sign informed consent form.
15. In the opinion of the Investigator, participants who are below their ideal body weight and would be unduly impacted by changes in their weight.
16. Known allergy to any of the drug planned to be given.
17. Arm B (S-PR): Serum total bilirubin \>1.5 \* ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
18. Arm C (S-PBR): Serum total bilirubin \>1.5 \* ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
19. Arm D (S-R-GemOx): Neuropathy Grade 2≥ (CTCAE, v5.0) interstitial lung disease or pulmonary fibrosis.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Karyopharm Therapeutics Inc
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Arizona
Tucson, Arizona, United States
California Cancer Associates for Research and Excellence
Encinitas, California, United States
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
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
US Oncology - Oncology Associates of Oregon
Eugene, Oregon, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
US Oncology - Prisma Health
Greenville, South Carolina, United States
US Oncology - Texas Oncology Austin Midtown
Austin, Texas, United States
University of Texas Southwestern
Dallas, Texas, United States
Baylor Clinic - Mcnair Center
Houston, Texas, United States
US Oncology - Northwest Cancer Specialists
Vancouver, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
XPORT-DLBCL-025
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.