- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05577364
Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients
A Single-arm, Multi-center, Phase Ib/II Study of Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients (Xplore Trial)
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to explore the maximum tolerated dose (MTD) of selinexor when combined with R-CHOP regimen for untreated EBV-positive DLBCL patients.
Phase Ib study:
Selinexor will be given orally at two different doses (40mg qw, and 60mg qw ) and combined with the R-CHOP regimen from the second cycle based on the "3+3" principle.
In the induction therapy period, 6 cycles of R-CHOP regimen and 2 cycles of rituximab in combination with selinexor are planned.
The dose limited toxicity (DLT) will be evaluated after the first cycle of selinexor in combination with R-CHOP.
Phase II study:
The phase II study of selinexor at recommended phase II dose (RP2D) dose level combined with R-CHOP regimen was conducted to explore the efficacy and safety of the combined regimen.
After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Qingqing Cai, MD. PhD.
- Phone Number: 0086-20-87342823
- Email: caiqq@sysucc.org.cn
Study Contact Backup
- Name: Huiqiang Huang, MD. PhD.
- Phone Number: 0086-20-87342823
- Email: huanghq@sysucc.org.cn
Study Locations
-
-
-
Shanghai, China, 200032
- Recruiting
- Fudan University Shanghai Cancer Center
-
Contact:
- Rong Tao, MD. PhD.
- Phone Number: 86-13651603660
- Email: taorong@xinhuamed.com.cn
-
-
Guangdong
-
Guangzhou, Guangdong, China, 51000
- Recruiting
- Sun Yat-sen Universitiy Cancer Center
-
Contact:
- Qing qing Cai, MD
- Phone Number: 0086-20-87342823
- Email: caiqq@sysucc.org.cn
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subjects fully understand and voluntarily participate in this study and sign informed consent
- Age ≥18, ≤70 years, no gender limitation.
- Histologically confirmed diagnosis of EBV-positive diffuse large B-cell lymphoma (DLBCL) (more than 50% of tumor cells are positive with EBV encoded small RNAs (EBERs) in situ hybridization were considered EBERs positive).
- Untreated patients, except for the short-time use of prednisone for controlling tumor-induced symptoms (no more than 30mg/d (or other equivalent amounts of other glucocorticoids), no more than 7 days).
- There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma: measurable lesion: Positron emission tomography/computed tomography (PET/CT) or CT and/or MRI, intranodal lesions with long diameter >1.5cm, and short diameter >1.0cm, or extranodal lesions with long diameter > 1.0 cm.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
- Expected survival ≥ 3 months.
Adequate function of bone marrow:
White blood cell ≥3.0×10E9/L, absolute neutrophil count ≥1.5×10E9/L Platelet ≥100×10E9/L (Bone marrow invasive patient≥75×109/L) Hemoglobin≥ 90g/L No granulocyte growth factor, platelet, or red blood cell transfusions were received within 14 days prior to examination.
Adequate function of the liver and renal:
Total bilirubin≤2×upper limit of normal (ULN) (patients with liver invasion or Gilbert syndrome ≤5×ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (patients with liver invasion ≤5×ULN) Serum creatinine ≤1.5×ULN or creatinine clearance rate ≥60 mL/min
- The patients agree to take effective contraceptive measures during the study period and till 12 months after the last administration of the study treatment.
Exclusion Criteria:
- EBV-positive DLBCL combined with other types of lymphoma. Transformed DLBCL.
- EBV-positive DLBCL with central nervous system invasion.
- The patients had previously received XPO1 inhibitors, such as selinexor and so on.
- The patients have contraindications to any drug in the combined treatment.
- The major surgery is performed within 4 weeks before enrollment, except for diagnosis.
- There are any life-threatening diseases, medical conditions or organ system dysfunction that the investigator believes may affect the safety or compliance of patients.
Heart function and disease meet one of the following conditions:
- Heart failure with the classification of New York Heart Association heart function of grade II;
- A history of unstable angina pectoris;
- A history of myocardial infarction within the past 1 years;
- Patients with clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
- A history of other malignant tumors within the past 5 years (except the cured cervical cancer and basal cell carcinoma of the skin).
- Patients with active bleeding.
- Uncontrolled infection exists within 7 days before treatment and parenteral antibiotics, antiviral drugs or antifungal drugs are needed; However, preventive use of these drugs (including parenteral anti-infective drugs) is allowed.
- Patients with chronic active hepatitis B or active hepatitis C. If the background hepatitis B Surface Antigen (HBsAg) and/or hepatitis B core Antibody (HBcAb) or hepatitis C Virus (HCV) antibody are positive, the further determination for Hepatitis B Virus (HBV) DNA (no more than 2500 copies /mL or 500 IU/mL) and HCV RNA (no more than the lower limit of the assay) can be included. The patients with HBsAg and/or HBcAb positive need to receive anti-HBV drugs.
- Patients with the infection of human immunodeficiency virus (HIV) and/or acquired Immunodeficiency syndrome.
- Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
- Pregnant and lactating women, and subjects of childbearing age who do not want to use contraception.
- Mentally ill persons or persons unable to obtain informed consent.
- The investigators think that the patient is not suitable for the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Selinexor in Combination With R-CHOP
Patients with untreated EBV-positive diffuse large B-cell lymphoma will receive sequentially higher doses of selinexor in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle).The initial dose of selinexor is 40mg qw po. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with selinexor will be conducted. |
Selinexor: 40mg qw po, and 60mg qw po (phase Ib); RP2D (II study); Selinexor is added from the second cycle of R-CHOP regimen.
Other Names:
Rituximab: 375mg/m2 iv.drip D1; Cyclophosphamide: 750mg/m2 iv.drip D1; Doxorubicin: 50mg/m2 iv.drip D1; Vincristine: 1.4g/m2 iv D1; Prednisone: 100mg po D1-5;
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose (MTD)
Time Frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
|
To identify the MDT
|
The first cycle of selinexor in combination with R-CHOP regimen (21 days)
|
Recommended Phase II Dose (RP2D)
Time Frame: The first cycle of selinexor in combination with R-CHOP regimen (21 days)
|
To identify the RP2D
|
The first cycle of selinexor in combination with R-CHOP regimen (21 days)
|
Complete response rate (CRR)
Time Frame: Up to 24 weeks.
|
To investigate the preliminary antitumor efficacy
|
Up to 24 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free survival (DFS)
Time Frame: From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
To investigate the preliminary antitumor efficacy
|
From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Objective response rate (ORR)
Time Frame: Up to 24 weeks.
|
To investigate the preliminary antitumor efficacy
|
Up to 24 weeks.
|
Progression-free survival (PFS)
Time Frame: From date of the first injection until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
To investigate the preliminary antitumor efficacy
|
From date of the first injection until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Overall survival (OS)
Time Frame: From date of the first injection until the date of death from ant cause, assessed up to 24 months
|
To investigate the preliminary antitumor efficacy
|
From date of the first injection until the date of death from ant cause, assessed up to 24 months
|
Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0
Time Frame: Through study completion, an average of 2 years.
|
To identify the incidence of AE and SAE
|
Through study completion, an average of 2 years.
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The correlation between EBV-DNA level and efficacy indicators, such as CRR, DFS, ORR, PFS, and OS
Time Frame: Through study completion, an average of 2 years.
|
To explore the correlation between EBV-DNA level and response
|
Through study completion, an average of 2 years.
|
The gene mutations such as DDX3X、TET2、PTPN2 and so on are sequenced by whole genome sequencing.
Time Frame: Through study completion, an average of 2 years.
|
To explore the correlations between gene mutations and response and prognosis.
|
Through study completion, an average of 2 years.
|
The mRNA and lncRNA alterations are sequenced by transcriptome sequencing.
Time Frame: Through study completion, an average of 2 years.
|
To explore the correlations between RNA alterations and response and prognosis.
|
Through study completion, an average of 2 years.
|
Immune-related indicators such as LAG-3, PD-1, PD-L1, TIGIF, CTLA-4, and so on are assessed by immunohistochemical (IHC) staining.
Time Frame: Through study completion, an average of 2 years.
|
To explore the correlations between immune-related indicators and response and prognosis.
|
Through study completion, an average of 2 years.
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Cyclophosphamide
- Prednisone
- Doxorubicin
- Vincristine
Other Study ID Numbers
- B2022-534-01
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on EBV-Positive Diffuse Large B-Cell Lymphoma, Nos
-
Huiqiang HuangRecruitingDiffuse Large B Cell Lymphoma | High-grade B-cell Lymphoma | Transformed Lymphoma | EBV-Positive DLBCL, Nos | ALK-Positive Anaplastic Large Cell Lymphoma | Follicular Lymphoma Grade IIIbChina
-
Huiqiang HuangRecruitingDiffuse Large B Cell Lymphoma | High-grade B-cell Lymphoma | Transformed Lymphoma | EBV-Positive DLBCL, Nos | ALK-Positive Anaplastic Large Cell Lymphoma | Follicular Lymphoma Grade IIIbChina
-
Huiqiang HuangRecruitingHigh-grade B-cell Lymphoma | Transformed Lymphoma | EBV-Positive DLBCL, Nos | ALK-Positive Anaplastic Large Cell Lymphoma | Non-GCB/ABC Diffuse Large B-Cell Lymphoma | Follicular Lymphoma Grade IIIbChina
-
Patrick C. Johnson, MDAstraZenecaRecruitingRefractory B-Cell Non-Hodgkin Lymphoma | Diffuse Large B-cell Lymphoma (DLBCL) | Grade 3b Follicular Lymphoma | Refractory Aggressive B-cell Lymphomas | Aggressive B-cell NHL | De Novo or Transformed Indolent B-cell Lymphoma | DLBCL, Nos Genetic Subtypes | T Cell/Histiocyte-rich Large B-cell Lymphoma and other conditionsUnited States
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingRecurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Recurrent Diffuse Large B-Cell... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingPlasmablastic Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Refractory High Grade B-Cell... and other conditionsUnited States
-
Centre Hospitalier Universitaire, AmiensInstitut Bergonié; Centre Henri Becquerel; Saint-Louis Hospital, Paris, France; Henri Mondor University Hospital and other collaboratorsRecruitingChemotherapy | Elderly | Diffuse Large B-Cell Lymphoma (DLBCL), NosFrance
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); AmgenActive, not recruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | CD20 Positive | Stage I Diffuse Large B-Cell Lymphoma | Stage II Diffuse Large B-Cell Lymphoma | Stage III Diffuse Large B-Cell Lymphoma | Stage IV Diffuse Large B-Cell LymphomaUnited States
-
National Cancer Institute (NCI)Active, not recruitingDiffuse Large B-Cell Lymphoma | High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements | Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Double-Expressor Lymphoma | EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | High Grade B-Cell Lymphoma, Not Otherwise... and other conditionsUnited States
-
National Cancer Institute (NCI)RecruitingLymphoplasmacytic Lymphoma | Ann Arbor Stage III Diffuse Large B-Cell Lymphoma | Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma | High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements | High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements | Grade 3b Follicular... and other conditionsUnited States
Clinical Trials on Selinexor
-
Karyopharm Therapeutics IncBelgium and Luxembourg Gynaecological Oncology Group; North-Eastern German... and other collaboratorsActive, not recruitingEndometrial CancerUnited States, China, Israel, Spain, Belgium, Germany, Greece, Czechia, Italy, Canada
-
Memorial Sloan Kettering Cancer CenterRecruitingSolid Tumor | Rhabdoid Tumor | Wilms Tumor | Nephroblastoma | Malignant Peripheral Nerve Sheath Tumors | MPNST | XPO1 Gene MutationUnited States
-
The First Hospital of Jilin UniversityRecruitingPTCL Patients Who Achieved Complete Response From Frontline TreatmentChina
-
University of RochesterKaryopharm Therapeutics IncRecruitingSmoldering Multiple MyelomaUnited States
-
Karyopharm Therapeutics IncGOG Foundation; European Network of Gynaecological Oncological Trial Groups... and other collaboratorsRecruitingEndometrial CancerUnited States, Belgium, Spain, Israel, Australia, Italy, Georgia, Ireland, Greece, Slovakia, Canada, Hungary, Czechia
-
University of UtahKaryopharm Therapeutics IncActive, not recruitingPrimary Myelofibrosis | Post-polycythemia Vera Myelofibrosis | Post-essential Thrombocythemia MyelofibrosisUnited States
-
Karyopharm Therapeutics IncCompletedHematological MalignanciesUnited States, Denmark, Canada
-
Karyopharm Therapeutics IncTerminatedRichter's TransformationUnited States, Germany, United Kingdom, Spain, Poland
-
Morten Mau-SoerensenHospices Civils de Lyon; Gustave Roussy, Cancer Campus, Grand Paris; Institut... and other collaboratorsUnknownThymoma | Advanced Thymic Epithelial TumourDenmark, France
-
Chunrui LiNanjing IASO Biotherapeutics Co.,LtdRecruitingExtramedullary Multiple MyelomaChina