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

NCT04442022 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: XPORT-DLBCL-0302020-000605-84
• Study Type: interventional
• Target: 501
• Locations: 6 countries
• Sites: 38

Brief 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.

Conditions

Relapsed/Refractory Diffuse Large B-cell Lymphoma

Keywords

Relapsed/Refractory DLBCL; Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP); Selinexor; Karyopharm; KCP-330; XPOVIO; DLBCL; XPORT-DLBCL-030; R-GDP

Outcome Measures

Primary Outcomes (2)

• Phase 2: Overall Response Rate (ORR): Based on Lugano Criteria 2014

  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

  From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)

Secondary Outcomes (13)

• Phase 2: Progression-free Survival: Based on Lugano Criteria 2014

  From date of initial randomization to the date of disease progression or death (maximum of 5 years from randomization)

• Phase 2: Overall Survival (OS)

  From date of initial randomization until death (maximum of 5 years from randomization)

• Phase 3: Overall Response Rate: Based on Lugano Criteria 2014

  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

  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

  From C1D1 (Cycles 1 up to 6; 21 days per cycle) up to 28 days after EoC therapy

Study Arms (6)

Phase 2: Selinexor 40 mg + R-GDP

EXPERIMENTAL

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); Drug: Rituximab (combination therapy); Drug: Gemcitabine (combination therapy); Drug: Dexamethasone (combination therapy); Drug: Cisplatin (combination therapy); Drug: Selinexor (continuous therapy)

Phase 2: Selinexor 60 mg + R-GDP

EXPERIMENTAL

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); Drug: Rituximab (combination therapy); Drug: Gemcitabine (combination therapy); Drug: Dexamethasone (combination therapy); Drug: Cisplatin (combination therapy); Drug: Selinexor (continuous therapy)

Phase 2: R-GDP

ACTIVE COMPARATOR

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); Drug: Gemcitabine (combination therapy); Drug: Dexamethasone (combination therapy); Drug: Cisplatin (combination therapy)

Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg

EXPERIMENTAL

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); Drug: Rituximab (combination therapy); Drug: Gemcitabine (combination therapy); Drug: Dexamethasone (combination therapy); Drug: Cisplatin (combination therapy); Drug: Selinexor (continuous therapy)

Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo

EXPERIMENTAL

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

Phase 3: Placebo + R-GDP followed by Placebo

PLACEBO COMPARATOR

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

Interventions

Selinexor (combination therapy) DRUG

Dose: 40 mg on Days 1 and 8 of each 21-day cycle for up to 6 cycles; Route of administration: oral

Phase 2: Selinexor 40 mg + R-GDP

Placebo matching for Selinexor (combination therapy) DRUG

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

Phase 3: Placebo + R-GDP followed by Placebo

Rituximab (combination therapy) DRUG

Dose: 375 milligram per meter square (mg/m\^2) on Day 1; Route of administration: intravenous (IV)

Phase 2: Selinexor 40 mg + R-GDP

Gemcitabine (combination therapy) DRUG

Dose: 1000 mg/m\^2 on Days 1 and 8; Route of administration: IV

Phase 2: R-GDP; Phase 2: Selinexor 40 mg + R-GDP; Phase 2: Selinexor 60 mg + R-GDP; Phase 3: Placebo + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg

Dexamethasone (combination therapy) DRUG

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

Phase 2: R-GDP; Phase 2: Selinexor 40 mg + R-GDP; Phase 2: Selinexor 60 mg + R-GDP; Phase 3: Placebo + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg

Cisplatin (combination therapy) DRUG

Dose: 75 mg/m\^2 on Day 1; Route of administration: IV

Phase 2: R-GDP; Phase 2: Selinexor 40 mg + R-GDP; Phase 2: Selinexor 60 mg + R-GDP; Phase 3: Placebo + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg

Selinexor (continuous therapy) DRUG

Dose: 60 mg QW for each 28-day cycle until PD; Route of administration: oral

Phase 2: Selinexor 40 mg + R-GDP; Phase 2: Selinexor 60 mg + R-GDP; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Selinexor 60 mg

Placebo matching for Selinexor (continuous therapy) DRUG

Dose: Placebo matching for 60 mg selinexor QW for each 28-day cycle until PD; Route of administration: oral

Phase 3: Placebo + R-GDP followed by Placebo; Phase 3: Selinexor (Selected Dose) + R-GDP followed by Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (38)

Ironwood Physicians P.C. dba Ironwood Cancer and Research Centers

Chandler, Arizona, 85224, United States

Location

Arizona Oncology Associates

Tucson, Arizona, 85711, United States

Location

The Oncology Institute (TOI) Clinical Research

Cerritos, California, 90703, United States

Location

Norton Cancer Institute, St. Matthews

Louisville, Kentucky, 40207, United States

Location

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Stony Brook

Stony Brook, New York, 11794, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

The University of Texas Health Science Center at Tyler DBA UT Health East Texas HOPE Cancer Center

Tyler, Texas, 75702, United States

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

Ruijin Hospital Affiliated to The Shanghai Jiao Tong University Medical School

Huangpu, Shanghai Municipality, 200025, China

Location

Zhongshan Hospital Fudan University

Xuhui, Shanghai Municipality, 200032, China

Location

Huaxi Hospital Sichuan University

Chengdu, Sichuan, 610044, China

Location

The first affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Assuta Ashdod Medical Center

Ashdod, 7747629, Israel

Location

Soroka Medical Center

Beersheba, 8457108, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Assuta medical centers - Ramat Hachayal

Tel Aviv, 6423906, Israel

Location

AOU Ospedali Riuniti-Università Politecnica delle Marche Clinica di Ematologia

Ancona, Ancona, 60020, Italy

Location

UOC Ematologia ad Indirizzo Oncologico, AORN "Sant'Anna e San Sebastiano"

Caserta, Caserta, 81100, Italy

Location

National Cancer Institute

Naples, Napoli, 1-80131, Italy

Location

AOU Maggiore della Carità SCDU Ematologia

Novara, Novara, 28100, Italy

Location

DIP. Oncologia- Ematologia, UOSD Centro Diagnosie TerapiaDei Linfomi

Pescara, Pescara, 65124, Italy

Location

Fondatione Policlinico Universitario A. Gemelli

Rome, Rome, 00168, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

Palermo, Sicily, 90146, Italy

Location

AOU City of Health and Science of Turin

Turin, Torino, 10126, Italy

Location

Pratia MCM Krakow

Krakow, Lesser, 30-510, Poland

Location

Szpitale pomorskie gdynia dept of haematology

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wrocławiu

Wroclaw, Radeckiego, 50-367, Poland

Location

Pratia Onkologia Katowice

Katowice, Silesian Voivodeship, 40-523, Poland

Location

CM Pratia Poznań

Skorzewo, Wielkopolska, 60819, Poland

Location

Institute of Hematology and Transfusion Medicine

Warsaw, 00-791, Poland

Location

Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, 02-781, Poland

Location

Institut català d'oncologia-hospital germans trias i pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Vall Hebron

Barcelona, Barcelona, 08035, Spain

Location

Institut Catala D'oncolocia

Barcelona, Barcelona, 09809, Spain

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Hospital Virgen del Rocío

Seville, Seville, 41013, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence

Interventions

selinexor; Combined Modality Therapy; Rituximab; Gemcitabine; Dexamethasone; Cisplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase 2 Portion of the Study: open label; Phase 3 Portion of the Study: double blinded
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2020
• First Posted: June 22, 2020
• Study Start: September 3, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

ES (5); CN (6); IL (4); IT (8); US (8); PL (7)