Combination Regimen of Teniposide, PD-1 Monoclonal Antibody and Selinixor for Patients With Relapsed or Refractory PCNSL

NCT07074470 | Recruiting

• 1 other identifier: 2024474
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy and safety of the VPX regimen, a novel combination of teniposide, PD-1 monoclonal antibody and selinexor, in patients with relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) who have progressed after high-dose methotrexate (HD-MTX)-based systemic therapy. By investigating this therapeutic approach, we seek to establish a new treatment paradigm that may improve clinical outcomes of this high-risk population.

Conditions

Primary Central Nervous System Lymphoma (PCNSL)

Keywords

VPX; PCNSL; teniposide; PD-1; selinexor

Outcome Measures

Primary Outcomes (1)

• Overall response rate(ORR)

  The rate of patients who achieved CR or PR after induction therapy with 2 cycles of VPX regimen

  At the end of 2 cycles of VPX regimen (each cycle is 21 days)

Secondary Outcomes (2)

• 2-year progression-free survival(PFS)

  From enrollment to 2-year after the end of last patient's treatment

• Major adverse events

  From enrollment to 1 month after induction therapy

Study Arms (2)

Cohort 1 (ASCT-eligible)

EXPERIMENTAL

Patients achieving response after 2 cycles of VPX regimen will proceed to ASCT as consolidation therapy followed by PD-1 monoclonal antibody therapy maintenance for up to 2 years, or until disease progression or unacceptable toxicity occurs.

Drug: Induction therapy-2 cycles of VPX (Teniposide, PD-1 monoclonal antibody plus Selinixor); Procedure: Consolidation therapy with ASCT after TB (Thiotepa plus Busulfan) preconditioning; Drug: Maintenance treatment-PD-1 monoclonal antibody

Cohort 2 (ASCT-ineligible)

EXPERIMENTAL

Patients achieving response after 2 cycles of VPX regimen will receive four additional cycles of VPX regimen, followed by whole-brain radiotherapy (WBRT) consolidation. After consolidation therapy, patients will receive PD-1 monoclonal antibody maintenance therapy for up to 2 years, or until disease progression or unacceptable toxicity occurs.

Drug: Induction therapy-2 cycles of VPX (Teniposide, PD-1 monoclonal antibody plus Selinixor); Drug: Consolidation therapy-4 cycles of VPX (Teniposide, PD-1 monoclonal antibody plus Selinixor); Radiation: Consolidation therapy-whole brain radiation therapy; Drug: Maintenance treatment-PD-1 monoclonal antibody

Interventions

Induction therapy-2 cycles of VPX (Teniposide, PD-1 monoclonal antibody plus Selinixor) DRUG

2 cycles of VPX regimen (21days per cycle) Teniposide: intravenous drip, 50mg d1-3; PD-1 monoclonal antibody: intravenous drip, 200mg d1; Selinixor: take 40mg orally, W1，60mg，W2，40mg biw，W3，cycle 1； 40mg， biw，cycle 2

Cohort 1 (ASCT-eligible); Cohort 2 (ASCT-ineligible)

Consolidation therapy with ASCT after TB (Thiotepa plus Busulfan) preconditioning PROCEDURE

TB preconditioning: Thiotepa intravenous drip 300mg/m2 d-6-d-5; Busulfan: intravenous drip, 0.8mg/kg q6h d-4--d2; followed by autologous peripheral stem cells infusion at day 0

Cohort 1 (ASCT-eligible)

Consolidation therapy-4 cycles of VPX (Teniposide, PD-1 monoclonal antibody plus Selinixor) DRUG

4 cycles of VPX regimen (21days per cycle) Teniposide: intravenous drip, 50mg d1-3; PD-1 monoclonal antibody: intravenous drip, 200mg d1; Selinixor: take 40mg orally biw, cycle 3-6；

Cohort 2 (ASCT-ineligible)

Consolidation therapy-whole brain radiation therapy RADIATION

whole brain radiotherapy: CTV1: 20-30Gy/10fractions GTVp: 25-40Gy/10fractions

Cohort 2 (ASCT-ineligible)

Maintenance treatment-PD-1 monoclonal antibody DRUG

PD-1 monoclonal antibody for up to 2 years intravenous infusion, 200mg d1 (21days per cycle)

Cohort 1 (ASCT-eligible); Cohort 2 (ASCT-ineligible)

Eligibility Criteria

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

You may qualify if:

• Age between 18 and 75 years old (inclusive).
• Participants must be able to understand and willing to sign a written informed consent form.
• The Eastern Cooperative Oncology Group is in a state of 0 to 3.
• The expected lifespan is ≥ 3 months (according to researchers).
• Primary central nervous system lymphoma of B-cell origin confirmed by pathology (histology or cytology).
• Measurable diseases are defined as having a short diameter of at least 1.0cm through enhanced MRI.
• Recurrent/refractory PCNSL: Must have received at least one systemic treatment based on high-dose methotrexate.
• Any non hematological toxicity related to previous treatment should be restored to grade 1 or normal (excluding hair loss according to NCI CTCAE 5.0).
• Bone marrow and organ function meet the following criteria (no blood transfusion, no G-CSF, no medication correction within 14 days prior to screening):
• Bone marrow function: absolute value of neutrophils ≥ 1.5 × 10 \^ 9/L, platelets ≥ 80 × 10 \^ 9/L, hemoglobin ≥ 80 g/L; Liver function: serum total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN, if there is liver metastasis); Glutamate oxalate transaminase (AST) and glutamate pyruvate transaminase (ALT) ≤ 2.5 × ULN (≤ 5.0 × ULN, if there is liver metastasis); Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time ≤ 1.5 × ULN; Renal function: serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance rate ≥ 60 mL/min (male: Cr (ml/min)=(140 years old) × body weight (kg)/72 × serum creatinine concentration (mg/dl); Female: Cr (ml/min)=(140 years old) x body weight (kg)/85 x serum creatinine concentration (mg/dl)
• Women with reproductive potential must agree to use efficient contraceptive methods during treatment and within 6 months after the last study drug administration. Sexually active males must agree to use highly effective contraceptive measures during treatment and within 6 months after the last dose of medication.
• Can accept multiple MRI/CT and lumbar puncture examinations.
• Swallowing oral tablets/capsules is not difficult.
• Good compliance, willing to follow inspection procedures such as visit schedule, medication schedule, laboratory tests, etc.

You may not qualify if:

• Chemotherapy, radiotherapy, immunotherapy, or antibody therapy for anti-tumor treatment, or herbal medicine with anti-tumor indications, small molecule targeted therapy within 2 weeks, monoclonal antibody conjugate drug or cytotoxic therapy within 10 weeks.
• Participate in another clinical study using the research product within 4 weeks prior to the first day of treatment.
• Patients who have used systemic corticosteroids for more than 5 days within 14 days prior to medication or require daily administration of\>10mg dexamethasone or equivalent medication to control central nervous system disorders.
• Active concurrent malignant tumors that require active treatment.
• Patients who have received previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, selenidazole, and tiniposide drugs within 6 months prior to initial administration.
• Suffering from uncontrolled or severe cardiovascular disease, including (but not limited to): any of the following: congestive heart failure (NYHA class III or IV); miocardial infarction; Unstable angina pectoris; Or there may be arrhythmia requiring treatment during screening, and the left ventricular ejection fraction (LVEF) within 6 months prior to initial administration is less than 50%; Primary cardiomyopathy (e.g. dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, undefined cardiomyopathy); A clinically significant medical history of QTc prolongation, grade II type II atrioventricular block or grade III atrioventricular block, or QTc interval (Method F)\>470 milliseconds (females) or\>480 milliseconds (males); Atrial fibrillation (EHRA ≥ 2b); Uncontrollable hypertensive patients are considered unsuitable to participate in this study.
• Uncontrolled infections or infections requiring intravenous antibiotic treatment.
• Chronic hepatitis B carriers with active hepatitis B or C infection (hepatitis B: acute hepatitis B, untreated chronic hepatitis B virus infection, HBV-DNA ≥ detection limit of each center; hepatitis C: HCV RNA positive) or syphilis. Attention: Non active carriers of HBV surface antigen (HBsAg), active HBV infection and persistent anti HBV suppression (HBV DNA\<detection limit per center) subjects, as well as HCV cured subjects, can be recruited.
• Human immunodeficiency virus (HIV) infection
• Clinically significant gastrointestinal abnormalities that may affect drug intake, transportation, or absorption (such as active gastrointestinal inflammation, chronic diarrhea, intestinal obstruction, etc.), or total gastrectomy or gastric banding surgery.
• Previous allogeneic stem cell transplantation. Or those who have the intention of allogeneic hematopoietic stem cell transplantation;
• For female participants, they are currently pregnant or breastfeeding.
• Allergic to research drugs or excipients.
• The patient has active mental illness, alcohol, drug or substance abuse.
• There are any life-threatening diseases, medical conditions, or organ system dysfunction that researchers believe may affect patient safety or compliance with research procedures.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Related Publications (2)

• Kasamon YL, Price LSL, Okusanya OO, Richardson NC, Li RJ, Ma L, Wu YT, Theoret M, Pazdur R, Gormley NJ. FDA Approval Summary: Selinexor for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Oncologist. 2021 Oct;26(10):879-886. doi: 10.1002/onco.13859. Epub 2021 Jul 1.

  PMID: 34132444 BACKGROUND

• Houillier C, Dureau S, Taillandier L, Houot R, Chinot O, Molucon-Chabrot C, Schmitt A, Gressin R, Choquet S, Damaj G, Peyrade F, Abraham J, Delwail V, Gyan E, Sanhes L, Cornillon J, Garidi R, Delmer A, Al Jijakli A, Morel P, Waultier A, Paillassa J, Chauchet A, Gastinne T, Laadhari M, Plissonnier AS, Feuvret L, Cassoux N, Touitou V, Ricard D, Hoang-Xuan K, Soussain C; LOC Network for CNS Lymphoma. Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study. J Clin Oncol. 2022 Nov 10;40(32):3692-3698. doi: 10.1200/JCO.22.00491. Epub 2022 Jul 14.

  PMID: 35834762 BACKGROUND

MeSH Terms

Interventions

Teniposide; Thiotepa; Busulfan

Intervention Hierarchy (Ancestors)

Glucosides; Glycosides; Carbohydrates; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Central Study Contacts

Zhengming Jin

CONTACT

67781856; jinzhengming519519@163.com

Changju Qu

CONTACT

67781856; qcj310@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 20, 2025
• Study Start: January 2, 2025
• Primary Completion (Estimated): January 2, 2030
• Study Completion (Estimated): January 2, 2032
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)