A Study of Selinexor with R-GDP for Relapsed/Refractory Diffuse Large B-cell Lymphoma
This study is looking at a treatment for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), which means the lymphoma has come back or didn't respond to previous treatments. It's testing a combination of drugs called selinexor and R-GDP (Rituximab, Gemcitabine, Dexamethasone, Platinum). The study aims to see how well this combination works and if it's safe for people who are not planning to have a stem cell transplant or CAR-T cell therapy. You might be able to join if you are 18 or older and have a confirmed diagnosis of DLBCL. The study will measure how many people respond to the treatment and how long they live without their disease getting worse, for up to 5 years.
- Study design
- This is a Phase 2/3 study, meaning it's testing different doses of selinexor and then comparing the best dose to a placebo. It plans to enroll 501 participants.
- What's involved
- You would receive selinexor (oral) or a matching placebo, along with Rituximab (IV), for up to 6 cycles, with each cycle lasting 21 days. If you respond, you might continue with selinexor alone.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your progress will be monitored for up to 5 years from the start of the study to see how long you live without your disease getting worse or needing new treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04442022
A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Active, Not Recruiting
PHASE2Ages 18+InterventionalTreatmentKaryopharm Therapeutics Inc
~501 participants
Updated 2026-07-02 on ClinicalTrials.gov
What's tested:Selinexor (combination therapy)Placebo matching for Selinexor (combination therapy)Rituximab (combination therapy)Gemcitabine (combination therapy)Dexamethasone (combination therapy)Cisplatin (combination therapy)
At a glance
Recruiting sites
0 of 38 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014
Measured over From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
+1 more outcome measured
Conditions
NCT04442022
Where you'd take part
This study runs at 38 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
AOU City of Health and Science of Turin
Turin, Torino, Italyno site contact published
AOU Maggiore della Carità SCDU Ematologia
Novara, Novara, Italyno site contact published
AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia
Ancona, Ancona, Italyno site contact published
Arizona Oncology Associates
Tucson, Arizonano site contact published
Assuta Ashdod Medical Center
Ashdod, Israelno site contact published
Assuta medical centers - Ramat Hachayal
Tel Aviv, Israelno site contact published
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Palermo, Sicily, Italyno site contact published
CM Pratia Poznań
Skorzewo, Wielkopolska, Polandno site contact published
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
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Eligibility criteria
Inclusion
Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided).
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
DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma \[NHL\]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma.
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).
What this trial measures
- Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014From 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 2014From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)