New pill combo aims to tackle tough lymphoma when other treatments fail
NCT ID NCT04442022
First seen Jun 26, 2026 · Last updated Jul 02, 2026 · Updated 2 times
Summary
This study tests whether adding the oral drug selinexor to standard chemotherapy (R-GDP) can help people with relapsed or refractory diffuse large B-cell lymphoma who cannot receive a stem cell transplant or CAR-T therapy. About 500 participants will receive either selinexor at one of two doses plus R-GDP, or a placebo plus R-GDP, for up to 6 cycles. The goal is to see if the combination improves response rates and delays cancer progression.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- selinexor (a targeted cancer drug taken as a pill)
- What this could lead to
- If successful, this could offer a new treatment option for patients with hard-to-treat diffuse large B-cell lymphoma who cannot have a stem cell transplant or CAR-T therapy.
- What could go wrong
- This is an early-to-mid stage trial, so the added benefit of selinexor is not yet proven. Side effects from the combination chemotherapy may be significant, and the drug may not improve outcomes enough to change standard care.
Why investors are watching
Karyopharm is testing its drug selinexor combined with a standard chemotherapy regimen in patients with relapsed or refractory diffuse large B-cell lymphoma who cannot receive stem cell transplants or CAR-T therapy. The trial has two phases: phase 2 picks the better of two selinexor doses, and phase 3 compares that dose against a placebo. For a micro-cap company, this readout could determine whether selinexor has a viable market in this patient group.
If it works: A positive result could mean Karyopharm has a new treatment option for a large group of lymphoma patients, potentially leading to regulatory approval and a new revenue source. The company could also gain credibility for its drug platform beyond this specific cancer.
If it fails: The trial could fail to show that adding selinexor improves outcomes, or the drug could cause safety problems that outweigh any benefit. Trials in this setting often fail, and a negative result would leave Karyopharm without a clear path forward for this indication.
AI-written from the trial record. Speculative, and not investment advice.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 2/3
Runs two stages together: whether the treatment works, then large-scale confirmation.
- Participants
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About 501 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Sep 2020
- Expected to finish
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Dec 2026
An estimate. End dates often move.
- Lead sponsor
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A company
The lead sponsor is a pharmaceutical, biotech, or medical-device company.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * 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. Exclusion Criteria: * 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). * Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events \[CTCAE\], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia. * 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.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
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AOU City of Health and Science of Turin
Turin, Torino, 10126, Italy
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AOU Maggiore della Carità SCDU Ematologia
Novara, Novara, 28100, Italy
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AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia
Ancona, Ancona, 60020, Italy
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Arizona Oncology Associates
Tucson, Arizona, 85711, United States
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Assuta Ashdod Medical Center
Ashdod, 7747629, Israel
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Assuta medical centers - Ramat Hachayal
Tel Aviv, 6423906, Israel
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Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Palermo, Sicily, 90146, Italy
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CM Pratia Poznań
Skorzewo, Wielkopolska, 60819, Poland
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DIP. Oncologia- Ematologia, UOSD Centro Diagnosie TerapiaDei Linfomi
Pescara, Pescara, 65124, Italy
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Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology
Warsaw, 02-781, Poland
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Fondatione Policlinico Universitario A. Gemelli
Rome, Rome, 00168, Italy
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Hospital Universitario La Paz
Madrid, Madrid, 28046, Spain
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Hospital Vall Hebron
Barcelona, Barcelona, 08035, Spain
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Hospital Virgen del Rocío
Seville, Seville, 41013, Spain
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Huaxi Hospital Sichuan University
Chengdu, Sichuan, 610044, China
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Institut Catala D'oncolocia
Barcelona, Barcelona, 09809, Spain
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Institut català d'oncologia-hospital germans trias i pujol
Badalona, Barcelona, 08916, Spain
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Institute of Hematology and Transfusion Medicine
Warsaw, 00-791, Poland
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Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
Chandler, Arizona, 85224, United States
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Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
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Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wrocławiu
Wroclaw, Radeckiego, 50-367, Poland
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National Cancer Institute
Naples, Napoli, 1-80131, Italy
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Norton Cancer Institute, St. Matthews
Louisville, Kentucky, 40207, United States
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Pratia MCM Krakow
Krakow, Lesser, 30-510, Poland
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Pratia Onkologia Katowice
Katowice, Silesian Voivodeship, 40-523, Poland
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Rabin Medical Center
Petah Tikva, 4941492, Israel
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Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School
Huangpu, Shanghai Municipality, 200025, China
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Soroka Medical Center
Beersheba, 8457108, Israel
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Stony Brook
Stony Brook, New York, 11794, United States
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Szpitale pomorskie gdynia dept of haematology
Gdynia, Pomeranian Voivodeship, 81-519, Poland
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Texas Oncology - Tyler
Tyler, Texas, 75702, United States
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The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215006, China
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The Oncology Institute (TOI) Clinical Research
Cerritos, California, 90703, United States
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The University of Texas Health Science Center at Tyler DBA UT Health East Texas HOPE Cancer Center
Tyler, Texas, 75702, United States
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The first affiliated Hospital, Zhejiang University
Hangzhou, Zhejiang, 310003, China
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UOC Ematologia ad Indirizzo Oncologico, AORN "Sant'Anna e San Sebastiano"
Caserta, Caserta, 81100, Italy
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University of Maryland Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201, United States
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Zhongshan Hospital Fudan University
Xuhui, Shanghai Municipality, 200032, China
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Other studies related to the condition(s) this trial covers.
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- Can a cancer drug reboot the immune system after a stem cell transplant?