AraC for Newly Diagnosed Adult Langerhans Cell Histiocytosis

Cytarabine Monotherapy for Adult Patients With Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study

Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder occurring in patients of all ages from neonates to the elderly. The current standard treatment protocol for children with de novo multisystem LCH is vinblastine plus prednisone. This regimen has never been proven effective for adults in a prospective study, since the only prospective trial evaluating the efficacy of a vinblastine/prednisone regimen in adults was prematurely closed due to unacceptable toxicities. A retrospective study showed an advantage for cytarabine monotherapy compared with vinblastine/prednisone in bone LCH patients. This phase 2, prospective, single-center study is designed to evaluate the efficacy and safety of cytarabine monotherapy in adults with newly diagnosed MS-LCH or LCH with multifocal single system (SS-m) involvement.

Study Overview

• Status: Recruiting
• Conditions: Langerhans Cell Histiocytosis
• Intervention / Treatment: Drug: Cytarabine

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

Contacts and Locations

• Study Contact: Name: Xinxin Cao, 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: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Histologically confirmed diagnosis of LCH.

  • Patients were newly diagnosed or did not receive prior systemic treatment of LCH (patients who had received radiotherapy alone were allowed).
  • 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 had received any treatment except radiotherapy for 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: AraC; cytarabine 100mg/m2 d1-5 subcutaneous	Drug: Cytarabine; cytarabine 100mg/m2 d1-5 subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Events were defined as a poor response to AraC, reactivation after AraC therapy and death from any cause.	the duration from initiation of AraC treatment to the date of a first 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 AraC therapy	on 12 months
Overall survival	Overall survival	the duration from initiation of AraC treatment to the date of death or last follow-up, assessed up to 5 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 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 10, 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; newly diagnosed; Langerhans cell histiocytosis
• 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; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: PUMCHNDLCH2

Drug and device information, study documents

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