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

NCT05698147 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: KY2022-881
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Central Nervous System Lymphoma

Keywords

Relapse refractory; Selinexor; ATG-010; Primary Central Nervous System Lymphoma（PCNSL）; Secondary Central Nervous System Lymphoma（SCNSL）

Outcome Measures

Primary Outcomes (3)

• Dose Escalation: Maximum Tolerated Dose (MTD) of Selinexor

  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

  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)

  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 Outcomes (4)

• Duration of Response (DOR)

  From first dose of study drug administration to end of treatment, up to 18 cycles(each cycle is 21 days)

• Overall Survival (OS)

  up to 12 months

• Progression-Free Survival (PFS)

  up to 12 months

• Number of Participants with Adverse Events

  From first dose of study drug administration to end of treatment (up to 18 cycles(each cycle is 21 days))

Other Outcomes (3)

• Gene mutations and frequency of 475 gene and whole exon

  At baseline

• The concentration of interleukin-10(IL-10)，interleukin-6(IL-6)，CXCL-13 cytokine in cerebrospinal fluid(CSF)

  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

  At the baseline, day 1 at cycle 3, 5 (21days/cycle), and every 3 months in the maintenance stage (up to 1 year))

Study Arms (1)

X-MTX-Ritu

EXPERIMENTAL

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; Drug: Rituximab; Drug: Methotrexate

Interventions

Selinexor DRUG

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.

Also known as: ATG-010

X-MTX-Ritu

Rituximab DRUG

Rituximab 375 mg/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.

Also known as: RiTUXimab Injection

X-MTX-Ritu

Methotrexate DRUG

high-dose Methotrexate 3.5 g/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.

Also known as: MTX

X-MTX-Ritu

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be able to understand and be willing to sign a written informed consent document.
• Men and woman who are 18-75 years old on the day of consenting to the study.
• Histologically documented PCNSL and SCNSL secondary to histologically documented systemic diffuse large B-cell lymphoma (DLBCL).
• Patients must have relapsed/refractory PCNSL or relapsed/refractory SCNSL.
• Patients must have response or remain stable disease for 2 months to prior methotrexate-based regimen.
• Patients who had prior autologous hematopoietic stem cell transplantation are eligible.
• 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.
• Participants must have an Eastern Cooperative Oncology Group performance status of 0-3.
• Participants must have adequate bone marrow and organ function shown by:
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
• 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
• International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal.
• 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.
• Calculated creatinine clearance(CrCl)≥50ml/min using the Cockcroft-Gault equation or 24-hour urine collection.

You may not qualify if:

• Patients with SCNSL actively receiving treatment for extra-CNS disease are excluded.
• Lymphoma patients with only intraocular involvement.
• Pathological diagnosis of PCNSL is T-cell lymphoma.
• Patients with disease progression within 6 months of prior methotrexate-containing regimen.
• patients only had received stereotactic radiation therapy as prior treatment.
• Patients have received chemotherapy, monoclonal antibodies or targeted anticancer therapy within 21 days or 5 half-lives, whichever is shorter, prior to C1D1.
• Patients with active, unstable cardiovascular diseases, fits any of the following:
• myocardial infarction within 6 months prior to the study enrollment
• unstable angina within 3 months prior to the study enrollment
• Uncontrolled clinically-significant conduction abnormalities (e.g., ventricular tachycardia, ventricular fibrillation, etc.)
• Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3
• Echocardiography showing left ventricular ejection fraction less than 50%
• Uncontrolled active infection within 1 week prior to the first dose of study drug.
• 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.
• Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.

Sponsors & Collaborators

• Tong Chen, MD: lead
• Antengene Corporation: collaborator

Study Sites (5)

The First Affiliated Hospital Of Anhui Medical University

Hefei, Anhui, China

NOT YET RECRUITING

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

NOT YET RECRUITING

The First Affiliated Hospital Of Fujian Medical University

Fuzhou, Fujian, China

NOT YET RECRUITING

Oncology Department of The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

NOT YET RECRUITING

Department of Hematology, Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

MeSH Terms

Interventions

selinexor; Rituximab; Methotrexate

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Tong Chen, Ph.D

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tong Chen, Ph.D

CONTACT

+862152887102; chentong@fudan.edu.cn

Yuan Yan, Ph.D

CONTACT

+862152888283; yuanyan@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief physician, professor

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 26, 2023
• Study Start: August 3, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)