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

March 19, 2024 updated by: Karyopharm Therapeutics Inc

A Phase 2/3, Multicenter Randomized Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

501

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Austria
      • Linz, Austria, 4021
        • Withdrawn
        • Kepler Universitaetskrankenhaus Med Campu III - Onkologie
      • Vienna, Austria, 1090
        • Withdrawn
        • University of Vienna, Medical Clinic I, Hematology
      • Vienna, Austria, 1130
        • Withdrawn
        • Hospital Hietzing
  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Completed
        • Jiangsu Province Hospital
      • Suzhou, Jiangsu, China, 215006
        • Completed
        • The First Affiliated Hospital Of Soochow University
    • Shanghai
      • Huangpu, Shanghai, China, 200025
        • Completed
        • Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School
      • Xuhui District, Shanghai, China, 200032
        • Completed
        • Zhongshan Hospital Fudan University
    • Sichuan
      • Chengdu, Sichuan, China, 610044
        • Completed
        • Huaxi Hospital Sichuan University
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310003
        • Completed
        • The First Affiliated Hospital, Zhejiang University
  • Israel
      • Ashdod, Israel, 7747629
        • Recruiting
        • Assuta Ashdod Medical Center
        • Contact:
        • Principal Investigator:
          • Merav Leiba, MD
      • Beer Sheva, Israel, 8457108
        • Recruiting
        • Soroka Medical Center
        • Contact:
        • Principal Investigator:
          • Itai Levi, MD
      • Haifa, Israel, 3109601
        • Withdrawn
        • Rambam health care campus (Department of Hematology & Bone Marrow Transplantation)
      • Holon, Israel, 5822012
        • Withdrawn
        • Wolfson Medical Center
      • Jerusalem, Israel, 9103401
        • Withdrawn
        • Hadassah Medical Center
      • Petach Tikva, Israel, 4941492
        • Recruiting
        • Rabin Medical Center
        • Principal Investigator:
          • Ronit Gurion, MD
        • Contact:
      • Tel Aviv, Israel, 6423906
        • Withdrawn
        • Sourasky Medical Center
      • Tel aviv, Israel, 6423906
        • Recruiting
        • Assuta medical centers - Ramat Hachayal
        • Contact:
        • Principal Investigator:
          • Ofer Shpilberg, MD
  • Italy
      • Ancona, Italy, 60020
        • Recruiting
        • AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia
        • Principal Investigator:
          • Guido Gini, MD
        • Contact:
      • Bologna, Italy, 40138
        • Not yet recruiting
        • AOU Policlinico S.Orsola Malpighi di Bologna, University of Bologna
        • Principal Investigator:
          • Pier Luigi Zinzani, MD
        • Contact:
      • Caserta, Italy, 81100
        • Recruiting
        • UOC Ematologia ad Indirizzo Oncologico, AORN "Sant'Anna e San Sebastiano"
        • Contact:
        • Principal Investigator:
          • Ferdinando Frigeri, MD
      • Novara, Italy, 28100
        • Recruiting
        • AOU Maggiore della Carità SCDU Ematologia
        • Principal Investigator:
          • Gianluca Gaidano, MD
        • Contact:
      • Pescara, Italy, 65124
        • Recruiting
        • DIP. Oncologia- Ematologia, UOSD Centro Diagnosie TerapiaDei Linfomi
        • Principal Investigator:
          • Elsa Pennese, MD
        • Contact:
      • Rome, Italy, 00168
        • Recruiting
        • Fondatione Policlinico Universitario A. Gemelli
        • Contact:
        • Principal Investigator:
          • Stefan Hohaus, MD
    • Napoli
      • Naples, Napoli, Italy, 1-80131
        • Recruiting
        • National Cancer Institute
        • Contact:
        • Principal Investigator:
          • Antonio Pinto, MD
    • Sicilia
      • Palermo, Sicilia, Italy, 90146
        • Recruiting
        • Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
        • Contact:
        • Principal Investigator:
          • Caterina Patti, MD
    • Torino
      • Turin, Torino, Italy, 10126
        • Not yet recruiting
        • AOU City of Health and Science of Turin
        • Principal Investigator:
          • Federica Cavallo, MD
        • Contact:
  • Poland
      • Warsaw, Poland, 00-791
        • Not yet recruiting
        • Institute of Hematology and Transfusion Medicine
        • Principal Investigator:
          • Ewa Lech-Maranda, MD
        • Contact:
      • Warszawa, Poland, 02-781
        • Recruiting
        • Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology
        • Principal Investigator:
          • Jan Walewski, MD
        • Contact:
    • Lesser
      • Krakow, Lesser, Poland, 30-510
        • Recruiting
        • Pratia MCM Krakow
        • Contact:
        • Principal Investigator:
          • Wojciech Jurczak, MD
    • Pomerania
      • Gdynia, Pomerania, Poland, 81-519
        • Recruiting
        • Szpitale pomorskie gdynia dept of haematology
        • Contact:
        • Principal Investigator:
          • Wanda Knopinska-Posluszny, MD
    • Radeckiego
      • Wroclaw, Radeckiego, Poland, 50-367
        • Recruiting
        • Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wrocławiu
        • Contact:
        • Principal Investigator:
          • Tomasz Wrobel
    • Wielkopolska
      • Skorzewo, Wielkopolska, Poland, 60819
        • Recruiting
        • CM Pratia Poznań
        • Principal Investigator:
          • Maciej Kazmierczak, MD
        • Contact:
    • Śląskie
      • Katowice, Śląskie, Poland, 40-523
        • Recruiting
        • Pratia Onkologia Katowice
        • Contact:
        • Principal Investigator:
          • Sebastian Grosicki
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Vall Hebron
        • Principal Investigator:
          • Pau Abrisqueta, MD
        • Contact:
      • Barcelona, Spain, 09809
        • Recruiting
        • Institut Catala D'oncolocia
        • Contact:
        • Principal Investigator:
          • Anna Sureda, MD
      • Madrid, Spain, 28046
        • Recruiting
        • Hospital Universitario La Paz
        • Contact:
        • Principal Investigator:
          • Victor Jiménez Yuste, MD
      • Seville, Spain, 41013
        • Recruiting
        • Hospital Virgen del Rocío
        • Contact:
        • Principal Investigator:
          • Fatima De la Cruz, MD
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Recruiting
        • Institut català d'oncologia-hospital germans trias i pujol
        • Contact:
        • Principal Investigator:
          • Juan Manuel Sancho, MD
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Recruiting
        • Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers
        • Contact:
        • Principal Investigator:
          • Sujith Kalmadi, MD
      • Tucson, Arizona, United States, 85711
        • Recruiting
        • Arizona Oncology Associates
        • Principal Investigator:
          • Sudhir Manda, MD
        • Contact:
    • California
      • Cerritos, California, United States, 90703
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Withdrawn
        • Investigative Clinical Research of Indiana, LLC
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Recruiting
        • Norton Cancer Institute, St. Matthews
        • Contact:
        • Principal Investigator:
          • Don Stevens, MD
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Withdrawn
        • Tulane Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Greenebaum Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Seung Tae Lee, MD
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Withdrawn
        • Comprehensive Cancer Centers of Nevada - Town Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • Withdrawn
        • New Mexico Cancer Care Alliance
    • New York
      • Stony Brook, New York, United States, 11794
    • Ohio
      • Canton, Ohio, United States, 44718
        • Withdrawn
        • Gabrail Cancer Center Research LLC
    • Texas
      • Dallas, Texas, United States, 75230
        • Withdrawn
        • Texas Oncology - Medical City Dallas
      • Dallas, Texas, United States, 75231
        • Withdrawn
        • Texas Oncology - Presbyterian Dallas Cancer Center
      • Dallas, Texas, United States, 75246
        • Withdrawn
        • Texas Oncology - Sammons
      • Fort Worth, Texas, United States, 76104
        • Withdrawn
        • Texas Oncology - Fort Worth
      • Plano, Texas, United States, 75075
        • Withdrawn
        • Texas Oncology - Plano East
      • Tyler, Texas, United States, 75702
        • Recruiting
        • Texas Oncology - Tyler
        • Principal Investigator:
          • Habte Yimer, MD
        • Contact:
      • Tyler, Texas, United States, 75702
        • Recruiting
        • The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center
        • Contact:
        • Principal Investigator:
          • Marc Usrey, MD
    • Washington
      • Everett, Washington, United States, 98201
        • Withdrawn
        • Providence Regional Cancer Partnership

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2: Selinexor 60 mg + R-GDP
Patients with RR DLBCL will receive combination therapy of selinexor 60 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.
Drug: 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
Drug: 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
Drug: 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
Drug: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
Drug: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV
Drug: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
Drug: 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
Drug: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV
Drug: Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Active Comparator: Phase 2: R-GDP
Patients with RR DLBCL will receive R-GDP on specified days (Days 1, 2, 3, 4, and 8) for each 21-day cycle for up to 6 cycles.
Drug: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
Drug: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV
Drug: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
Drug: 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
Drug: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV
Experimental: Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg
Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by selinexor 60 mg orally QW for each 28-day cycle until PD or unacceptable toxicity.
Drug: 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
Drug: 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
Drug: 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
Drug: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
Drug: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV
Drug: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
Drug: 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
Drug: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV
Drug: Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral
Experimental: Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo
Patients with RR DLBCL will receive combination therapy of selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.
Drug: 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
Drug: 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
Drug: 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
Drug: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
Drug: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV
Drug: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
Drug: 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
Drug: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV
Drug: 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
Placebo Comparator: Phase 3: Placebo + R-GDP followed by Placebo
Patients with RR DLBCL will receive combination therapy of placebo matching for selinexor (selected dose from Phase 2) at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by matching placebo for selinexor orally QW for each 28-day cycle until PD or unacceptable toxicity.
Drug: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
Drug: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV
Drug: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
Drug: 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
Drug: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV
Drug: 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
Drug: 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
Experimental: Phase 2: Selinexor 40 mg + R-GDP
Patients with RR DLBCL will receive combination therapy of selinexor 40 mg orally at Day 1 and Day 8 of each 21-day cycle for up to 6 cycles in combination with R-GDP followed by single-agent continuous therapy with selinexor 60 mg orally once weekly (QW) for each 28-day cycle until progressive disease (PD) or unacceptable toxicity.
Drug: 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
Drug: 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
Drug: 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
Drug: Rituximab (combination therapy)
Dose: 375 milligram per meter square (mg/m^2) on Day 1; Route of administration: intravenous (IV)
Drug: Rituximab (combination therapy)
Dose: 375 mg/m^2 on Day 1; Route of administration: IV
Drug: Gemcitabine (combination therapy)
Dose: 1000 mg/m^2 on Days 1 and 8; Route of administration: IV
Drug: 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
Drug: Cisplatin (combination therapy)
Dose: 75 mg/m^2 on Day 1; Route of administration: IV
Drug: Selinexor (continuous therapy)
Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014
Time Frame: From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
From 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 2014
Time Frame: From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase 2: Overall Survival (OS)
Time Frame: From date of initial randomization until death (maximum of 5 years from randomization)
From date of initial randomization until death (maximum of 5 years from randomization)
Phase 2: Overall Response Rate at the End of Combination Therapy (ORR-EoC): Based on Lugano Criteria 2014
Time Frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 2: Duration of Response (DOR): Based on Lugano Criteria 2014
Time Frame: From time of first response until disease progression or death (maximum of 5 years from randomization)
From time of first response until disease progression or death (maximum of 5 years from randomization)
Phase 2: Number of Patients with Adverse Events (AEs)
Time Frame: Up to 30 days after last dose of study drug (maximum of 5 years from randomization)
Up to 30 days after last dose of study drug (maximum of 5 years from randomization)
Phase 2: Progression-free Survival: Based on Lugano Criteria 2014
Time Frame: From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Phase 3: Overall Response Rate: Based on Lugano Criteria 2014
Time Frame: From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
From date of initial randomization to the date of disease progression or initiating a new DLBCL treatment (maximum of 5 years from randomization)
Phase 3: Overall Survival
Time Frame: From date of initial randomization until death (maximum of 5 years from randomization)
From date of initial randomization until death (maximum of 5 years from randomization)
Phase 2: Overall Response Rate at the End of Combination Therapy: Based on Modified Lugano Criteria
Time Frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 3: Overall Response Rate at the End of Combination Therapy: Based on Lugano Criteria 2014
Time Frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 3: Overall Response Rate at the End of Combination Therapy: Based on Modified Lugano Criteria
Time Frame: From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy
Phase 3: Duration of Response: Based on Lugano Criteria 2014
Time Frame: From time of first response until disease progression or death (maximum of 5 years from randomization)
From time of first response until disease progression or death (maximum of 5 years from randomization)
Phase 3: Progression-free Survival: Based on Modified Lugano Criteria
Time Frame: From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)
Phase 3: Number of Patients with Adverse Events
Time Frame: Up to 30 days after last dose of study drug (maximum of 5 years from randomization)
Up to 30 days after last dose of study drug (maximum of 5 years from randomization)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karyopharm Therapeutics Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 3, 2020

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 10, 2020

First Submitted That Met QC Criteria

June 18, 2020

First Posted (Actual)

June 22, 2020

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XPORT-DLBCL-030
  • 2020-000605-84 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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