Thalidomide, Cyclophosphamide and Dexamethasone for Recurrent/Refractory Adult Langerhans Cell Histiocytosis

NCT04120519 | Unknown Phase 2

• 1 other identifier: PUMCHRRLCH-1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder occurring most commonly in children. Because of the rarity of LCH in adults and a lack of prospective randomized trials, the treatment strategy for adults is mostly based on pediatric protocols. The overall response rate of therapy based on vinblastine plus prednisone in adults is lower than in children and the treatment tends to show higher toxicity.There is little data to guide therapy after frontline treatment. In a phase 2 trial, thalidomide as monotherapy gave a 70% response rate in recurrent/refractory low risk LCH but there were no responses in six high risk children. We want to analyze the efficacy and toxicity of thalidomide combined with dexamethasone and cyclophosphamide regimens in the treatment of recurrent/refractory LCH among adult patients at our hospital.

Conditions

Langerhans Cell Histiocytosis

Keywords

Langerhans cell histiocytosis; adult; recurrent/refractory

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  Events were defined as a poor response to TCD, reactivation after TCD therapy and death from any cause.

  the duration from initiation of treatment to the date of first documented event or date of death from any cause, whichever come first, assessed up to 5 years

Secondary Outcomes (2)

• Overall response rate

  on 12 months

• Overall survival

  the duration from initiation of TCD treatment to the date of death or last follow-up, assessed up to 5 years

Study Arms (1)

TCD

EXPERIMENTAL

thalidomide 100mg qn cyclophosphamide 300mg/m2 d1,8,15 dexamethasone 40mg d1,8,15,22

Drug: thalidomide combined with dexamethasone and cyclophosphamide

Interventions

thalidomide combined with dexamethasone and cyclophosphamide DRUG

TCD

TCD

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of LCH.
• Patients were recurrent/refractory or at least receive one line of systemic treatment of LCH
• Age ≥18 years and ≤75 years.
• LCH involved multisystem or multifocal single system.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Patients must have adequate renal, liver, and bone marrow function as defined by the following criteria:
• Absolute neutrophil count ≥1500 cells per mm3 or ≥500 cells per mm3 in the case of known hematopoietic system involvement by LCH.
• Platelet count ≥100000 cells per mm3 or ≥20000 cells per mm3 in the case of known hematopoietic system involvement by LCH.
• Creatinine clearance \[according to Cockcroft formula\] ≥60 mL/min.
• Aspartate aminotransferase and alanine aminotransferase ≤2·5×upper limit of normal \[ULN\], and total bilirubin ≤2·5×ULN; or ≤10×ULN in the case of known liver involvement by LCH.
• No active or untreated infection.
• No cardiac abnormalities.
• Subject provide written informed consent.
• A female is eligible to enter and participate in this study if she is of:
• Non-childbearing potential including ω Any female who has had a surgical procedure rendering her incapable of becoming pregnant.

You may not qualify if:

• Non-langerhans cell histiocytosis.
• Patients had concurrent malignancies.
• Patients who were newly diagnosed LCH.
• History of myocardial infarction, or unstable angina, or New York Heart Association (NYHA) Grade III-IV within 6 months prior to Day 1.
• Women who were pregnant or of childbearing potential.
• Known HIV seropositive, active hepatitis C infection, and/or hepatitis B (defined as HCV RNA
• ≥103 copies or HBV DNA ≥103 copies at screening).
• Major surgical procedure within 28 days prior to the first dose of study treatment.
• Presence of uncontrolled infection.
• Evidence of active bleeding or bleeding diathesis.
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell; Recurrence

Interventions

Dexamethasone; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jian Li

  Peking Union Medical College Hospital

  STUDY DIRECTOR

Central Study Contacts

Xinxin caoyang, MD

CONTACT

69155027; caoxinxin@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: thalidomide combined with dexamethasone and cyclophosphamide

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: October 9, 2019
• Study Start: October 10, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: June 8, 2021

Record last verified: 2021-06

Locations

CN (1)