Efficacy and Safety of XTD Regimen (Selinexor, Thalidomide and Dexamethasone) in Adult Patients With Relapsed/Refractory LCH

Efficacy and Safety of XTD Regimen (Selinexor, Thalidomide and Dexamethasone) in Adult Patients With Relapsed/Refractory Langerhans Cell Histiocytosis: A Prospective, Multicenter, Single-Arm Study.

In adult patients with relapsed/refractory Langerhans cell histiocytosis (LCH), a treatment regimen of XTD regimen (Selinexor, Thalidomide and Dexamethasone) is planned to be used.

Study Overview

• Status: Active, not recruiting
• Conditions: Langerhans Cell Histiocytosis (LCH)
• Intervention / Treatment: Drug: Selinexor; Drug: Thalidomide (100mg); Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, beijing,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Organ pathology confirmed diagnosis of LCH;
• Age 18 years or older;
• Multi-system involvement, or single system with multiple lesions;
• Disease not relieved after receiving at least one systemic treatment, or disease relapsed after improvement;
• ECOG performance status score ≤2;
• Clinical physician determines suitability for this treatment protocol;
• Subjects can understand the study protocol and are willing to participate in this study, providing written informed consent.

Exclusion Criteria:

• Single system single lesion LCH
• Underwent major surgery within 4 weeks prior to the first administration of the study drug;
• Underwent radiotherapy within 4 weeks prior to the first administration of the study drug;
• History of myocardial infarction within the past year; suffers from New York Heart Association (NYHA) class 3 or 4 congestive heart failure, or has a history of NYHA class 3 or 4 congestive heart failure, unless left ventricular ejection fraction (LVEF) ≥ 50% in the echocardiogram (ECHO) screening performed within 1 month before entering the study;
• Pregnant or breastfeeding women (women of childbearing age with positive pregnancy test at baseline or who have not undergone pregnancy testing. Postmenopausal women must have been menopausal for at least 12 months);
• Abnormal liver and kidney function: creatinine level ≥176.8μmol/l (2mg/dl), transaminase and bilirubin levels more than 2 times the upper limit of normal (for LCH patients with liver involvement, transaminase levels more than 10 times and bilirubin levels more than 3 times the upper limit of normal);
• Severe hematological abnormalities: absolute neutrophil count less than 1 × 10^9/L, platelet less than 50×10^9/L;
• Presence of uncontrolled infections;
• Any other circumstances that the investigator believes to be inappropriate for the patient to participate in this trial;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adult patients with relapsed or refractory LCH; (1) Relapsed or refractory LCH; (2) Age ≥ 18 years; (3) Multi-focal single system or multi-system involvement; (4) ECOG PS 0-2 score

Drug: Selinexor; The combined treatment period includes 12 cycles: receiving Selinexor (60mg, D1, 8, 15, 22), Thalidomide (100mg, D1-28), and Dexamethasone (40mg, D1, 8, 15, 22) as oral treatment, with each cycle lasting 28 days, for a total of 12 cycles of combined treatment, or until disease progression, death, or occurrence of intolerable toxicity. Alternatively, until disease progression, death, or occurrence of intolerable toxicity.; Drug: Thalidomide (100mg); The combined treatment period includes 12 cycles: receiving Selinexor (60mg, D1, 8, 15, 22), Thalidomide (100mg, D1-28), and Dexamethasone (40mg, D1, 8, 15, 22) as oral treatment, with each cycle lasting 28 days, for a total of 12 cycles of combined treatment, or until disease progression, death, or occurrence of intolerable toxicity. Alternatively, until disease progression, death, or occurrence of intolerable toxicity.; Drug: Dexamethasone; The combined treatment period includes 12 cycles: receiving Selinexor (60mg, D1, 8, 15, 22), Thalidomide (100mg, D1-28), and Dexamethasone (40mg, D1, 8, 15, 22) as oral treatment, with each cycle lasting 28 days, for a total of 12 cycles of combined treatment, or until disease progression, death, or occurrence of intolerable toxicity. Alternatively, until disease progression, death, or occurrence of intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	PFS defined as the time from XTD initiation to first documented disease progression, relapse after XTD, death from any cause, or last follow-up.	From enrollment to the end of treatment at 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	The overall response rate (ORR) was defined as the cumulative proportion of patients attaining either a complete response (CR) or partial response (PR) .	From enrollment to the end of treatment at 8 weeks
OS	OS was measured from XTD initiation to death or last follow-up	From enrollment to the end of treatment at 8 weeks
Adverse Events	Toxicities were recorded and graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	From enrollment to the end of treatment at 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fact-G	The score of Functional Assessment of Cancer Therapy - General	From enrollment to the end of treatment at 8 weeks
Correlation between the positivity of NGS in MAPK pathway and therapeutic efficacy/PFS	Correlation between the positivity of NGS in MAPK pathway and therapeutic efficacy/PFS	From enrollment to the end of treatment at 8 weeks

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 2, 2027

Study Registration Dates

• First Submitted: September 24, 2025
• First Submitted That Met QC Criteria: September 24, 2025
• First Posted (Estimated): October 2, 2025

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lymphatic Diseases; Lung Diseases, Interstitial; Histiocytosis; Hemic and Lymphatic Diseases; Histiocytosis, Langerhans-Cell; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Dexamethasone; Thalidomide; selinexor
• Other Study ID Numbers: NCCH0027

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: No
• Studies a U.S. FDA-regulated device product: No