RECRUITING

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

Conditions

Relapsed/refractory Diffuse Large B-cell Lymphoma Relapsed/Refractory DLBCL Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP)Selinexor Karyopharm KCP-330 XPOVIO DLBCL XPORT-DLBCL-030 R-GDP

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2020-09-03

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04442022

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Karyopharm Medical Information

CONTACT

(888) 209-9326

clinicaltrials@karyopharm.com

Study Locations (Sites)

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

Chandler, Arizona, 85224

United States

Arizona Oncology Associates

Tucson, Arizona, 85711

United States

The Oncology Institute (TOI) Clinical Research

Cerritos, California, 90703

United States

Investigative Clinical Research of Indiana, LLC

Indianapolis, Indiana, 46260

United States

Norton Cancer Institute, St. Matthews

Louisville, Kentucky, 40207

United States

Tulane Cancer Center

New Orleans, Louisiana, 70112

United States

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201

United States

Comprehensive Cancer Centers of Nevada - Town Center

Las Vegas, Nevada, 89169

United States

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106

United States

Stony Brook

Stony Brook, New York, 11794

United States

Gabrail Cancer Center Research LLC

Canton, Ohio, 44718

United States

Texas Oncology - Medical City Dallas

Dallas, Texas, 75230

United States

Texas Oncology - Presbyterian Dallas Cancer Center

Dallas, Texas, 75231

United States

Texas Oncology - Sammons

Dallas, Texas, 75246

United States

Texas Oncology - Fort Worth

Fort Worth, Texas, 76104

United States

Texas Oncology - Plano East

Plano, Texas, 75075

United States

Texas Oncology - Tyler

Tyler, Texas, 75702

United States

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

Tyler, Texas, 75702

United States

Providence Regional Cancer Partnership

Everett, Washington, 98201

United States

Collaborators and Investigators

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 Registration Dates

Study Start Date2020-09-03

Study Completion Date2025-12

Study Record Updates

Study Start Date2020-09-03

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Relapsed/refractory Diffuse Large B-cell Lymphoma