Selinexor in Combination With R-CHOP Followed by Selinexor Maintenance for Untreated EBV-positive DLBCL Patients

December 13, 2023 updated by: Qingqing Cai, Sun Yat-sen University

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)

This is a prospective, single-arm, multi-center, phase Ib/II clinical trial to evaluate the safety, tolerability, and efficacy of selinexor in combination with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by selinexor maintenance for untreated EBV-positive diffuse large B-cell lymphoma (DLBCL) patients.

Study Overview

Status

Recruiting

Conditions

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

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 2
  • Phase 1

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 Contact Backup

Study Locations

  • China
      • Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 51000
        • Recruiting
        • Sun Yat-sen Universitiy Cancer Center
        • Contact:

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 to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Subjects fully understand and voluntarily participate in this study and sign informed consent
  2. Age ≥18, ≤70 years, no gender limitation.
  3. 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).
  4. 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).
  5. 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.
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2.
  7. Expected survival ≥ 3 months.

  8. 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.

  9. 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

  10. 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:

  1. EBV-positive DLBCL combined with other types of lymphoma. Transformed DLBCL.
  2. EBV-positive DLBCL with central nervous system invasion.
  3. The patients had previously received XPO1 inhibitors, such as selinexor and so on.
  4. The patients have contraindications to any drug in the combined treatment.
  5. The major surgery is performed within 4 weeks before enrollment, except for diagnosis.
  6. There are any life-threatening diseases, medical conditions or organ system dysfunction that the investigator believes may affect the safety or compliance of patients.

  7. Heart function and disease meet one of the following conditions:

    1. Heart failure with the classification of New York Heart Association heart function of grade II;
    2. A history of unstable angina pectoris;
    3. A history of myocardial infarction within the past 1 years;
    4. Patients with clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;
  8. A history of other malignant tumors within the past 5 years (except the cured cervical cancer and basal cell carcinoma of the skin).
  9. Patients with active bleeding.
  10. 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.
  11. 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.
  12. Patients with the infection of human immunodeficiency virus (HIV) and/or acquired Immunodeficiency syndrome.
  13. Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
  14. Pregnant and lactating women, and subjects of childbearing age who do not want to use contraception.
  15. Mentally ill persons or persons unable to obtain informed consent.
  16. The investigators think that the patient is not suitable for the study.

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: 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.
Drug: Selinexor

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:
  • exportin 1 (XPO1) inhibitor
Drug: R-CHOP Protocol

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:
  • Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

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

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

Sponsor

Sun Yat-sen University

Collaborators

Fudan University
Antengene Corporation

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)

November 1, 2022

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

February 28, 2026

Study Registration Dates

First Submitted

October 6, 2022

First Submitted That Met QC Criteria

October 9, 2022

First Posted (Actual)

October 13, 2022

Study Record Updates

Last Update Posted (Estimated)

December 14, 2023

Last Update Submitted That Met QC Criteria

December 13, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • B2022-534-01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

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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