Selinexor With ICE Chemotherapy in Secondary Central Nervous System Involving B-cell Non-Hodgkin Lymphoma

NCT06552559 | Recruiting Phase 1 DMC

• 1 other identifier: CISL2301
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

Secondary involvement of the central nervous system (CNS), such as CNS relapse after treatment or progression during treatment, is a rare but deadly occurrence in patients with B-cell non-Hodgkin lymphoma (NHL), particularly in cases of diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (FL). Despite the grim prognosis associated with secondary CNS involvement, no definitive treatment strategy exists. Selinexor®, an oral, first-in-class, potent selective inhibitor of nuclear export that binds to XPO1, leads to the nuclear retention of tumor suppressor and growth regulator proteins, as well as topoisomerase II enzymes, thereby restoring their functions. Preclinical studies have also shown that selinexor can sensitize cancer cells to topoisomerase inhibitors, alkylating agents, and steroids. Selinexor has been approved by the Food and Drug Administration for relapsed or refractory DLBCL. We hypothesize that selinexor could work synergistically with ifosfamide (an alkylating agent) and etoposide (a topoisomerase II inhibitor) in the ifosfamide, carboplatin, and etoposide (ICE) regimen. High-dose dexamethasone was added to this regimen to enhance the efficacy of ICE as a salvage regimen for secondary CNS involvement, due to its ability to cross the blood-brain barrier. This phase I/II study aims to evaluate the efficacy and safety of selinexor in combination with ifosfamide, carboplatin, etoposide (ICE), and dexamethasone in patients with relapsed or refractory B-cell non-Hodgkin lymphoma with secondary CNS involvement.

Conditions

B-cell Lymphoma Recurrent; B-cell Lymphoma Refractory; CNS Metastases

Keywords

Non-Hodgkin B-cell lymphoma; Secondary CNS involvement; Selinexor; ICE

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of elinexor in phase 1

  Maximum tolerated dose and recommended phase 2 dose level of Selinexor combined with ifosfamide, carboplatin, etoposide and dexamethasone

  Up to 1 year

• Objective response rate

  Complete and partial response out of participants in phase 2

  Up to 2 years

Secondary Outcomes (1)

• Duration of response

  Uo to 3 years

Study Arms (1)

Selinexor plus ICED

EXPERIMENTAL

Phase 1 part of the study: Treatment will be repeated every three weeks. * Selinexor: DL1 (40mg)/DL2 (60mg)/DL3 (80mg) PO, day 3, 5, 7 * Ifosfamide 1500 mg/m(2) infused over 2 h on days 1-3 * Carboplatin (5 AUC) on day 1 * Etoposide 100 mg/m(2) on days 1-3 * Dexamethasome 40 mg PO or IV on days 1-4 Phase 2 part of the study: Treatment will be repeated every three weeks. * Selinexor: MTD (determined by phase 1 part of the study) PO, day 3, 5, 7 * Ifosfamide 1500 mg/m(2) infused over 2 h on days 1-3 * Carboplatin (5 AUC) on day 1 * Etoposide 100 mg/m(2) on days 1-3 * Dexamethasome 40 mg PO or IV on days 1-4

Drug: Selinexor

Interventions

Selinexor DRUG

Combination chemotherapy

Also known as: Ifosfamide, carboplatin, etoposide, dexamethasone

Selinexor plus ICED

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed B-cell NHL with CNS involvement DLBCL including ABC, GCB or PMBCL subtypes Indolent lymphomas transformed to aggressive lymphomas Follicular lymphomas
• Patients must have received at least one cycles of anthracycline based chemotherapy administered with curative intent
• Patients must be age ≥18 years.
• Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
• Patients must have ECOG performance status of 0-2.
• Patients must have laboratory test results within these ranges: Absolute neutrophil count ≥ 1500/mm³, Platelet count ≥ 100,000/mm³, Serum creatinine clearance ≥40 mL/min, Total bilirubin ≤ 1.5x ULN (Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.), AST (SGOT) and ALT (SGPT) ≤ 2x ULN
• Women of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test prior to selinexor treatment. Male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential.
• Patients must be able to understand and willing to sign a written informed consent document.
• Patients must be able to adhere to the study visit schedule and other protocol requirements.
• Patients must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Patients with hepatitis B virus including HBsAg-positive carrier or IgG anti- HBc-positive can be enrolled if they can receive anti-viral prophylaxis

You may not qualify if:

• Patients with primary CNS lymphoma
• Patients with a prior history with selinexor

Sponsors & Collaborators

• Samsung Medical Center: lead
• Korean Society of Hematology: collaborator

Study Sites (2)

Samsung Cancer Research Institute

Seoul, 135-710, South Korea

RECRUITING

Samsung Medical Center

Seoul, 135-710, South Korea

RECRUITING

MeSH Terms

Interventions

selinexor; Ifosfamide; Carboplatin; Etoposide; Dexamethasone

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Seok Jin Kim

  Samsung Medical Center

  STUDY CHAIR

Central Study Contacts

Seok Jin Kim, MD., PhD

CONTACT

82234101766; kstwoh@skku.edu

Ka Young Song, MD

CONTACT

songga0e@naver.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Phase 1/2 study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with secondary central nervous system involving relapsed or refractory B-cell non-Hodgkin lymphoma: a single arm, open label, multicentre study

Study Record Dates

• First Submitted: August 3, 2024
• First Posted: August 14, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (2)