Selinexor in Combination With MTX+Ritu to Treat R/R CNSL

September 13, 2025 updated by: Tong Chen, MD

Selinexor in Combination With Methotrexate and Rituximab for Relapsed /Refractory Central Nervous System (CNS) Lymphoma

This is a single-arm and open-label study to explore X+MTX+Ritu (ATG-010, Methotrexate, Rituximab) regimen in Relapse refractory PCNSL patients. Approximately 30 patients will be enrolled in the study. In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen and escalating doses of oral ATG-010 weekly in a 3+3 design. Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen （Methotrexate 3.5 g/m2, d1; Rituximab 375 mg/m2, d0）and escalating doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60, 80 and 100mg respectively respectively on day 1,8,15,22 for 28-days cycle.

The phase 2 expansion at the recommended dose level based on phase 1b trial. The total 6 cycles, 28 days per cycle . And, Subjects participating in the study will undergo a screening period（up to 21days）, a treatment period, and a follow-up period. The screening period is a maximum of 21 days before treatment period, And will be followed by 6 cycles of combination treatment（28 days per cycle）.

partial remission(PR) patients after induction treatment will continue ATG-010 maintenance up to 1 year or until disease progression, intolerable toxicity, death.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China
        • Not yet recruiting
        • The First Affiliated Hospital of Anhui Medical University
        • Contact:
          • Jian Ge, Ph.D
    • Beijing Municipality
      • Beijing, Beijing Municipality, China
        • Not yet recruiting
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China
        • Not yet recruiting
        • The First Affiliated Hospital of Fujian Medical University
        • Contact:
          • Zhiyong Zeng, Ph.D
    • Henan
      • Zhengzhou, Henan, China, 450052
        • Not yet recruiting
        • Oncology Department of The First Affiliated Hospital of Zhengzhou University
        • Contact:
        • Principal Investigator:
          • Mingzhi Zhang, PhD
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200040
        • Recruiting
        • Department of Hematology, Huashan Hospital, Fudan University
        • Contact:
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

    1. Participants must be able to understand and be willing to sign a written informed consent document.
    2. Men and woman who are 18-75 years old on the day of consenting to the study.
    3. Histologically documented PCNSL and SCNSL secondary to histologically documented systemic diffuse large B-cell lymphoma (DLBCL).
    4. Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL.
    5. Patients must have response or remain stable disease for 2 months to prior methotrexate-based regimen.
    6. Patients who had prior autologous hematopoietic stem cell transplantation are eligible.
    7. Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI of the brain or head CT) 28 days prior to cycle1 day 1(C1D1). For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells.
    8. Participants must have an Eastern Cooperative Oncology Group performance status of 0-3.

    9. Participants must have adequate bone marrow and organ function shown by:

      1. Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L
      2. Platelets ≥ 75 x 10^9/L and no platelet transfusion within the past 14 days prior to study registration c Hemoglobin (Hgb) ≥ 8 g/dL and no red blood cell (RBC) transfusion within the past 14 days prior to study registration
    10. International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal.
    11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal.
    12. Serum bilirubin ≤ 1.5 times the upper limit of normal; or total bilirubin ≤ 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome.
    13. Calculated creatinine clearance(CrCl)≥50ml/min using the Cockcroft-Gault equation or 24-hour urine collection.
    14. Life expectancy of > 3 months.

Exclusion Criteria:

  1. Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
  2. Lymphoma patients with only intraocular involvement.
  3. Pathological diagnosis of PCNSL is T-cell lymphoma.
  4. Patients with disease progression within 6 months of prior methotrexate-containing regimen.
  5. patients only had received stereotactic radiation therapy as prior treatment.
  6. Patients have received chemotherapy, monoclonal antibodies or targeted anticancer therapy within 21 days or 5 half-lives, whichever is shorter, prior to C1D1.

  7. Patients with active, unstable cardiovascular diseases, fits any of the following:

    1. myocardial infarction within 6 months prior to the study enrollment
    2. unstable angina within 3 months prior to the study enrollment
    3. Uncontrolled clinically-significant conduction abnormalities (e.g., ventricular tachycardia, ventricular fibrillation, etc.)
    4. Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3
    5. Echocardiography showing left ventricular ejection fraction less than 50%
  8. Uncontrolled active infection within 1 week prior to the first dose of study drug.
  9. Known active hepatitis B, or C infection or HIV infection; Note: Hepatitis B virus (HBV) surface antigen (HBsAg) and or hepatitis B core antibody-positive but undetectable HBV DNA or Hepatitis C virus (HCV) antibody positive but hepatitis C virus RNA undetectable are allowed.
  10. Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
  11. Prior exposure to a selective inhibitor of nuclear export(SINE) compound, including selinexor.
  12. Serious, active psychiatric, or medical conditions which, in the opinion of the Investigator, could interfere with 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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: X-MTX-Ritu

Escalating doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60, 80 and 100mg respectively respectively on day 1,8,15,22 for 28-days cycle.and the phase 2 expansion at the recommended dose level based on phase 1b trial. And，

Methotrexate 3.5 g/m2, d1 and Rituximab 375 mg/m2, d0, 28-days cycle.The total 6 cycles, 28 days per cycle.
Drug: Selinexor

Selinexor dose escalation: 60,80,100mg respectively on day 1,8,15,22 for 28 days cycles, and dose expansion at the RP2D of Selinexor.

PR patients after induction treatment will continue ATG-010 maintenance up to 1 year or until disease progression, intolerable toxicity, death.

Other Names:
  • ATG-010
Drug: Rituximab
Rituximab 375 mg/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.
Other Names:
  • RiTUXimab Injection
Drug: Methotrexate
high-dose Methotrexate 3.5 g/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.
Other Names:
  • MTX

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose Escalation: Maximum Tolerated Dose (MTD) of Selinexor
Time Frame: Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days)
The MTD will be determined by study definition as the highest dose level without significant safety and tolerability concern.
Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days)
Dose Escalation: Recommended Phase 2 Does (RP2D) of Selinexor
Time Frame: Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days)
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy data collected during the dose escalation portion of the study
Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days)
Objective Response Rate (ORR)
Time Frame: Cycle 1 Day 1 (each cycle consists of maximum 21 days) until a CR, CRu or PR (up to 18 cycles(each cycle is 21 days)).
ORR is defined as the proportion of patients with a best response of Complete remission (CR) or Unconfirmed(CRu), or PR during induction therapy
Cycle 1 Day 1 (each cycle consists of maximum 21 days) until a CR, CRu or PR (up to 18 cycles(each cycle is 21 days)).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: From first dose of study drug administration to end of treatment, up to 18 cycles(each cycle is 21 days)
Duration from the first observation of at least PR to time of progressive disease(PD), or deaths due to disease progression,whichever occurs first
From first dose of study drug administration to end of treatment, up to 18 cycles(each cycle is 21 days)
Overall Survival (OS)
Time Frame: up to 12 months
Occurrence of death regardless of cause
up to 12 months
Progression-Free Survival (PFS)
Time Frame: up to 12 months
Duration from start of study treatment to PD or death (regardless of cause), whichever comes first
up to 12 months
Number of Participants with Adverse Events
Time Frame: From first dose of study drug administration to end of treatment (up to 18 cycles(each cycle is 21 days))
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
From first dose of study drug administration to end of treatment (up to 18 cycles(each cycle is 21 days))

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Gene mutations and frequency of 475 gene and whole exon
Time Frame: At baseline
The types of gene mutations and frequency of tumor are measured by whole exon sequencing via NGS(next-generation sequencing).
At baseline
The concentration of interleukin-10(IL-10)，interleukin-6(IL-6)，CXCL-13 cytokine in cerebrospinal fluid(CSF)
Time Frame: At the baseline, day 1 at cycle 3, 5 (21 days/cycle), and every 3 months in the maintenance stage (up to 1 year))
The levels of cytokines will be analyzed by flow cytometry
At the baseline, day 1 at cycle 3, 5 (21 days/cycle), and every 3 months in the maintenance stage (up to 1 year))
Circulating tumor DNA (ctDNA) in the CSF
Time Frame: At the baseline, day 1 at cycle 3, 5 (21days/cycle), and every 3 months in the maintenance stage (up to 1 year))
The levels of ctDNA will be analyzed by next-generation sequencing.
At the baseline, day 1 at cycle 3, 5 (21days/cycle), and every 3 months in the maintenance stage (up to 1 year))

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tong Chen, MD

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Antengene Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tong Chen, Ph.D, Huashan Hospital

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 3, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 4, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 26, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 16, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KY2022-881

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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