Relapsed or Refractory Diffuse Large B-Cell LymphomaPhase 1/2NCT04607772
Study of Selinexor in Combination With Backbone Treatments or Novel Therapies In Participants With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)
A Phase 1/2 study testing Selinexor, Rituximab and Bendamustine in people with Relapsed or Refractory Diffuse Large B-Cell Lymphoma, run by Karyopharm Therapeutics Inc at 18 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- Selinexor, Rituximab and Bendamustine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 18 sitesUnited States
- Study dates
- 18 Nov 2020to Dec 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants greater than or equal to (≥) 18 years of age.
- Have pathologically confirmed relapsed/refractory (RR) DLBCL, not otherwise specified (NOS).
- Participants with High Grade B-cell Lymphoma (HGBL) are allowed in Phase 2 only.
- 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.
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- 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.
- Adequate bone marrow function at Screening.
- Circulating lymphocytes less than or equal to (≤) 50 * 109/L.
- Adequate liver and kidney function.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- An estimated life expectancy of >6 months at Screening.
- 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).
- 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).
- 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).
- 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.
Who cannot join
- DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma; composite lymphoma (Hodgkin lymphoma + NHL); Gray zone lymphoma; DLBCL transformed from Chronic Lymphocytic Leukemia (Richter Syndrome); Primary mediastinal large B-cell lymphoma (PMBCL); T-cell rich large B-cell lymphoma.
- Previous treatment with selinexor or other XPO1 inhibitors.
- Contraindication to any drug contained in the different treatment arms.
- 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.
- 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.
- 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.
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- Major surgery <14 days of C1D1.
- 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).
- 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).
- 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.
- 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).
- Inability to swallow tablets, malabsorption syndrome, or any other GI disease or dysfunction that could interfere with absorption of study treatment.
- Breastfeeding women or pregnant women.
- Inability or unwillingness to sign informed consent form.
- In the opinion of the Investigator, participants who are below their ideal body weight and would be unduly impacted by changes in their weight.
- Known allergy to any of the drug planned to be given.
- The following are Arm Specific exclusion criteria:
- Arm B (S-PR): Serum total bilirubin >1.5 * ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
- Arm C (S-PBR): Serum total bilirubin >1.5 * ULN, Neuropathy Grade ≥2 (CTCAE, v5.0).
- Arm D (S-R-GemOx): Neuropathy Grade 2≥ (CTCAE, v5.0) interstitial lung disease or pulmonary fibrosis.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
US Oncology - Rocky Mountain Cancer Center
Aurora, Colorado, 80012
US Oncology - Texas Oncology Austin Midtown
Austin, Texas, 78705
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263
University of Texas Southwestern
Dallas, Texas, 75390
Mission Cancer + Blood
Des Moines, Iowa, 50309
Karmanos Cancer Institute
Detroit, Michigan, 48021
California Cancer Associates for Research and Excellence
Encinitas, California, 92024
US Oncology - Oncology Associates of Oregon
Eugene, Oregon, 97401
US Oncology - Prisma Health
Greenville, South Carolina, 29605
Baylor Clinic - Mcnair Center
Houston, Texas, 77030
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Loyola University Medical Center
Maywood, Illinois, 60153
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of California Irvine
Orange, California, 92868
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
University of Arizona
Tucson, Arizona, 85724
US Oncology - Northwest Cancer Specialists
Vancouver, Washington, 98684
About this study
Official title: A Multicenter, Phase 1/2 Study of Selinexor in Combination With Backbone Treatments or Novel Therapies in Patients With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)
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.
- Being tested
- Selinexor, Rituximab, Bendamustine, Polatuzumab Vedotin, Ibrutinib
- Keywords
- Karyopharm, Diffuse Large B-Cell Lymphoma, DLBCL, KPT-330, Selinexor, Bendamustine, Rituximab, Polatuzumab Vedotin, Gemcitabine, Oxaliplatin, Ibrutinib, Lenalidomide, Tafasitamab, Venetoclax
- Medical subject headings
- Recurrence, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SelinexorDrug
Also called KPT-330
Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg)
RituximabDrug
Dose: 375 mg/m^2
BendamustineDrug
Dose: 90 mg/m^2
Polatuzumab VedotinDrug
Dose: 1.8 mg/kg
IbrutinibDrug
Dose: 420, 560 mg
LenalidomideDrug
Dose: 20, 25 mg
TafasitamabDrug
Dose: 12 mg/kg
VenetoclaxDrug
Dose: 200, 400, 600, 800 mg
GemcitabineDrug
Dose: 1000 mg/m^2
OxaliplatinDrug
Dose: 100 mg/m^2
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Selinexor with Bendamustine and Rituximab (S-BR)) | Experimental | 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. Receives: Drug: Selinexor; Drug: Rituximab; Drug: Bendamustine |
| Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR) | Experimental | 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. Receives: Drug: Selinexor; Drug: Rituximab; Drug: Polatuzumab Vedotin |
| Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR) | Experimental | 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. Receives: Drug: Selinexor; Drug: Rituximab; Drug: Bendamustine; Drug: Polatuzumab Vedotin |
| Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx) | Experimental | 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. Receives: Drug: Selinexor; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin |
| Arm E: Selinexor with Ibrutinib and Rituximab (S-IR) | Experimental | 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. Receives: Drug: Selinexor; Drug: Rituximab; Drug: Ibrutinib |
| Arm F: Selinexor with Lenalidomide and Rituximab (S-LR) | Experimental | 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. Receives: Drug: Selinexor; Drug: Rituximab; Drug: Lenalidomide |
| Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT) | Experimental | 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. Receives: Drug: Selinexor; Drug: Lenalidomide; Drug: Tafasitamab |
| Arm H: Selinexor with Venetoclax (S-V) | Experimental | 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. Receives: Drug: Selinexor; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose (MTD)
Measured: Within the first cycle (maximum 28 days) of treatment
Phase 1: Recommended Phase 2 Dose (RP2D)
Measured: Up to 6 cycles (up to 6 months) of treatment
Phase 2: Overall Response Rate (ORR) per the Lugano Classification 2014
Measured: Cycle 1 Day 1 (each cycle consists of maximum 28 days) until a complete response (CR) or partial response (PR) (up to 6 months)
Secondary outcomes (9)
Phase 1: Overall Response Rate per the Lugano Classification 2014
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: From start of study drug administration up to 30 days after last dose of study treatment (up to 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2020
- Study start18 Nov 2020
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04607772
- Sponsor's protocol ID
- XPORT-DLBCL-025
- Status last verified
- Sep 2025
- First submitted
- 26 Oct 2020
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Phase 1/2 Study of Selinexor in Combination With Backbone Treatments or Novel Therapies in Patients With Relapsed or Refractory (RR) Diffuse Large B-Cell Lymphoma (DLBCL)
- ClinicalTrials.gov ID
- NCT04607772
- Acronym / sponsor ID
- XPORT-DLBCL-025
- Keywords
- Karyopharm, Diffuse Large B-Cell Lymphoma, DLBCL, KPT-330, Selinexor, Bendamustine, Rituximab, Polatuzumab Vedotin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Karyopharm Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2020 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 29 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Arm A: Selinexor with Bendamustine and Rituximab (S-BR)) | Experimental | Drug: Selinexor, Drug: Rituximab, Drug: BendamustineParticipants 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. |
| Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR) | Experimental | Drug: Selinexor, Drug: Rituximab, Drug: Polatuzumab VedotinParticipants 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. |
| Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR) | Experimental | Drug: Selinexor, Drug: Rituximab, Drug: Bendamustine, Drug: Polatuzumab VedotinParticipants 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. |
| Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx) | Experimental | Drug: Selinexor, Drug: Rituximab, Drug: Gemcitabine, Drug: OxaliplatinParticipants 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. |
| Arm E: Selinexor with Ibrutinib and Rituximab (S-IR) | Experimental | Drug: Selinexor, Drug: Rituximab, Drug: IbrutinibParticipants 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. |
| Arm F: Selinexor with Lenalidomide and Rituximab (S-LR) | Experimental | Drug: Selinexor, Drug: Rituximab, Drug: LenalidomideParticipants 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. |
| Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT) | Experimental | Drug: Selinexor, Drug: Lenalidomide, Drug: TafasitamabParticipants 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. |
| Arm H: Selinexor with Venetoclax (S-V) | Experimental | Drug: Selinexor, Drug: VenetoclaxParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Participants greater than or equal to (≥) 18 years of age.
- Have pathologically confirmed relapsed/refractory (RR) DLBCL, not otherwise specified (NOS).
- Participants with High Grade B-cell Lymphoma (HGBL) are allowed in Phase 2 only.
- Prior lines of systemic therapy for the treatment of DLBCL:
- 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.
Key exclusion criteria (20 listed)
- DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma; composite lymphoma (Hodgkin lymphoma + NHL); Gray zone lymphoma; DLBCL transformed from Chronic Lymphocytic Leukemia (Richter Syndrome); Primary mediastinal large B-cell lymphoma (PMBCL); T-cell rich large B-cell lymphoma.
- Previous treatment with selinexor or other XPO1 inhibitors.
- Contraindication to any drug contained in the different treatment arms.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SelinexorAlso: KPT-330Dose: 40 mg (2 tablets of 20 mg), 60 mg (3 tablets of 20 mg), 80 mg (4 tablets of 20 mg) | Drug | Arm A: Selinexor with Bendamustine and Rituximab (S-BR)), Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR), Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR), Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx), Arm E: Selinexor with Ibrutinib and Rituximab (S-IR), Arm F: Selinexor with Lenalidomide and Rituximab (S-LR), Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT), Arm H: Selinexor with Venetoclax (S-V) |
| RituximabDose: 375 mg/m^2 | Drug | Arm A: Selinexor with Bendamustine and Rituximab (S-BR)), Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR), Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR), Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx), Arm E: Selinexor with Ibrutinib and Rituximab (S-IR), Arm F: Selinexor with Lenalidomide and Rituximab (S-LR) |
| BendamustineDose: 90 mg/m^2 | Drug | Arm A: Selinexor with Bendamustine and Rituximab (S-BR)), Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR) |
| Polatuzumab VedotinDose: 1.8 mg/kg | Drug | Arm B: Selinexor with Polatuzumab Vedotin and Rituximab (S-PR), Arm C: Selinexor, Polatuzumab Vedotin, Bendamustine, Rituximab (S-PBR) |
| IbrutinibDose: 420, 560 mg | Drug | Arm E: Selinexor with Ibrutinib and Rituximab (S-IR) |
| LenalidomideDose: 20, 25 mg | Drug | Arm F: Selinexor with Lenalidomide and Rituximab (S-LR), Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT) |
| TafasitamabDose: 12 mg/kg | Drug | Arm G: Selinexor with Lenalidomide and Tafasitamab (S-LT) |
| VenetoclaxDose: 200, 400, 600, 800 mg | Drug | Arm H: Selinexor with Venetoclax (S-V) |
| GemcitabineDose: 1000 mg/m^2 | Drug | Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx) |
| OxaliplatinDose: 100 mg/m^2 | Drug | Arm D: Selinexor, Rituximab, Gemcitabine, Oxaliplatin (S-R-GemOx) |
Primary outcome
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)
9 secondary outcomes
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
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)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Selinexor, Rituximab and Bendamustine in people with Relapsed or Refractory Diffuse Large B-Cell Lymphoma, run by Karyopharm Therapeutics Inc at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Maximum Tolerated Dose (MTD) (time frame: Within the first cycle (maximum 28 days) of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2025.