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Clinical Trials in the USA / NCT04442022
Active, not recruiting Phase 2/3

A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma

NCT04442022 · tracked via the Priya Life Science USA tracker
Sponsor
Karyopharm Therapeutics Inc
Phase
Phase 2/3
Started
2020-09-03
Last updated
2026-07-02

Condition(s) studied

Relapsed/Refractory Diffuse Large B-cell Lymphoma

Investigational drug(s) / intervention(s)

Selinexor (combination therapy)Selinexor (combination therapy)Selinexor (combination therapy)Placebo matching for Selinexor (combination therapy)Rituximab (combination therapy)Rituximab (combination therapy)Gemcitabine (combination therapy)Dexamethasone (combination therapy)Cisplatin (combination therapy)Selinexor (continuous therapy)Placebo matching for Selinexor (continuous therapy)

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

Study summary

The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram \[mg\] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
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.

Primary outcome measure(s)

Trial sites (38)

FacilityCityRegionStatus
Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers Chandler Arizona
Arizona Oncology Associates Tucson Arizona
The Oncology Institute (TOI) Clinical Research Cerritos California
Norton Cancer Institute, St. Matthews Louisville Kentucky
University of Maryland Greenebaum Comprehensive Cancer Center Baltimore Maryland
Stony Brook Stony Brook New York
Texas Oncology - Tyler Tyler Texas
The University of Texas Health Science Center at Tyler DBA UT Health East Texas HOPE Cancer Center Tyler Texas
Jiangsu Province Hospital Nanjing Jiangsu
The First Affiliated Hospital of Soochow University Suzhou Jiangsu
Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School Huangpu Shanghai Municipality
Zhongshan Hospital Fudan University Xuhui Shanghai Municipality
Huaxi Hospital Sichuan University Chengdu Sichuan
The first affiliated Hospital, Zhejiang University Hangzhou Zhejiang
Assuta Ashdod Medical Center Ashdod Israel
Soroka Medical Center Beersheba Israel
Rabin Medical Center Petah Tikva Israel
Assuta medical centers - Ramat Hachayal Tel Aviv Israel
AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia Ancona Ancona
UOC Ematologia ad Indirizzo Oncologico, AORN "Sant'Anna e San Sebastiano" Caserta Caserta
National Cancer Institute Naples Napoli
AOU Maggiore della Carità SCDU Ematologia Novara Novara
DIP. Oncologia- Ematologia, UOSD Centro Diagnosie TerapiaDei Linfomi Pescara Pescara
Fondatione Policlinico Universitario A. Gemelli Rome Rome
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello Palermo Sicily
AOU City of Health and Science of Turin Turin Torino
Pratia MCM Krakow Krakow Lesser
Szpitale pomorskie gdynia dept of haematology Gdynia Pomeranian Voivodeship
Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wrocławiu Wroclaw Radeckiego
Pratia Onkologia Katowice Katowice Silesian Voivodeship
CM Pratia Poznań Skorzewo Wielkopolska
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
Hospital Vall Hebron Barcelona Barcelona
Institut Catala D'oncolocia Barcelona Barcelona
Hospital Universitario La Paz Madrid Madrid
Hospital Virgen del Rocío Seville Seville
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04442022 on ClinicalTrials.gov ↗ ← All trials in the USA