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

Thalidomide, Cyclophosphamide and Dexamethasone for Adult Patients With Recurrent/Refractory Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study

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.

Study Overview

• Status: Recruiting
• Conditions: Langerhans Cell Histiocytosis
• Intervention / Treatment: Drug: thalidomide combined with dexamethasone and cyclophosphamide

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xinxin caoyang, MD; Phone Number: 69155027; Email: caoxinxin@pumch.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Xinxin Cao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • 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.

ω Subjects have experienced total cessation of menses for more than 1 year and be greater than 45 years in age.

⎫ Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, and agrees to use adequate contraception.

• Male subjects must use an effective barrier method of contraception during the study and for 90 days following the last course of MA if sexually active with a childbearing potential

Exclusion Criteria:

• • 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.

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: TCD; thalidomide 100mg qn cyclophosphamide 300mg/m2 d1,8,15 dexamethasone 40mg d1,8,15,22	Drug: thalidomide combined with dexamethasone and cyclophosphamide; TCD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	the cumulative number of patients with either non-active disease or regressive disease (signs and symptoms were improved with no new lesions) after TCD therapy	on 12 months
Overall survival	Overall survival	the duration from initiation of TCD treatment to the date of death or last follow-up, assessed up to 5 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Jian Li, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: October 8, 2019
• First Posted (Actual): October 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: adult; Langerhans cell histiocytosis; recurrent/refractory
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lymphatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Histiocytosis, Langerhans-Cell; Histiocytosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Cyclophosphamide; Thalidomide
• Other Study ID Numbers: PUMCHRRLCH-1

Drug and device information, study documents

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