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

Sponsor
Samsung Medical Center
Study ID
NCT06552559
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
May 1, 2024
Status verified
Apr 2026
Primary completion
Dec 30, 2028
Completion
Dec 30, 2028

Study Design

Enrollment
37 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Selinexor plus ICED
    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

Primary Outcome Measure

Maximum tolerated dose of elinexor in phase 1 [ Time Frame: Up to 1 year ]

Central Contacts

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