Langerhans Cell Histiocytosis (LCH)
Conditions
Brief summary
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.
Interventions
DRUGSelinexor
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.
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.
DRUGDexamethasone
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.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A multicenter, prospective, interventional study, with a planned number of subjects: approximately 40 cases.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From enrollment to the end of treatment at 8 weeks | PFS defined as the time from XTD initiation to first documented disease progression, relapse after XTD, death from any cause, or last follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | From enrollment to the end of treatment at 8 weeks | The overall response rate (ORR) was defined as the cumulative proportion of patients attaining either a complete response (CR) or partial response (PR) . |
| OS | From enrollment to the end of treatment at 8 weeks | OS was measured from XTD initiation to death or last follow-up |
| Adverse Events | From enrollment to the end of treatment at 8 weeks | Toxicities were recorded and graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlation between the positivity of NGS in MAPK pathway and therapeutic efficacy/PFS | From enrollment to the end of treatment at 8 weeks | Correlation between the positivity of NGS in MAPK pathway and therapeutic efficacy/PFS |
| Fact-G | From enrollment to the end of treatment at 8 weeks | The score of Functional Assessment of Cancer Therapy - General |
Countries
China
Outcome results
None listed