LCH-IV: Clinical Trial for Children and Adolescents with Langerhans Cell Histiocytosis

International Collaborative Treatment Protocol for Children and Adolescents with Langerhans Cell Histiocytosis

Category:

Histiocytic Disorders

Diseases Treated:

Langerhans cell histiocytosis

Eligibility Overview:

  • Diagnosis of Langerhans cell histiocytosis
  • Younger than 18 years old
  • Meets inclusion criteria for the respective stratum

 

  1. Brief Summary

    Langerhans cell histiocytosis[aa1]  (LCH) is a rare disorder of the immune system that may affect many different organs, including the skeleton, skin, lymph nodes, liver, lungs, spleen, hematopoietic system, and central nervous system (CNS).

    There are two widely recognized disease extent categories:

    • Single-system LCH (involvement of a single organ or system)
    • Multisystem LCH (involvement of 2 or more organ systems)

    Patients with single-system LCH (SS-LCH) of the skeleton, skin, or the lymph nodes have an excellent prognosis and are felt to need a minimum or sometimes even no treatment at all. The course of multisystem LCH (MS-LCH) is unpredictable upon diagnosis, ranging from spontaneous resolution to fulminant progression and fatal outcome. Involvement of crucial organs like the hematopoietic system, liver or spleen is associated with a poor prognosis.

    Recent large clinical trials have shown the response to initial treatment is a highly important prognostic factor. Patients with MS-LCH without involvement of “risk organs” have very high probability of survival when treated with a standard regimen consisting of vinblastine and steroids. In contrast, involvement of risk organs carries the risk of unfavorable outcome.

    The international efforts of the past 20 years have shown that combination therapy with vinblastine and prednisone is an effective therapy for MS-LCH. The previous prospective trial LCH-III confirmed this regimen as a standard regimen for MS-LCH in patients with and without risk organ involvement. It also showed that prolonged treatment in the latter group (treatment duration of 12 vs. 6 months) is superior in preventing disease reactivations. The LCH-IV study seeks to tailor treatment based on features at presentation and on response to treatment. St. Jude Children’s Research Hospital is a participating site for five of the seven strata.

    Primary Objectives

    • To decrease MS-LCH mortality in patients with risk organ involvement, who do not respond to front-line therapy, by an early switch to a more intensive treatment
    • To reduce reactivation rates and permanent consequences in MS-LCH by prolonging and intensifying continuation treatment
    • To reduce reactivation rates and permanent consequences in a subset of SS-LCH patients by prolonging continuation therapy
    • To investigate the value of a uniform second-line therapy with prednisone, cytarabine, and vincristine, followed by randomized continuation therapy in patients with non-risk organ LCH
    • To evaluate the value of cladribine (2--chlorodeoxyadenosine ) in patients with isolated tumorous CNS-LCH
    • To evaluate whether systemic therapy with intravenous immunoglobulin (IVIG) or low-dose cytarabine can improve neuropsychological symptoms in patients with clinically manifested neurodegenerative CNS-LCH.
    • To describe the spectrum and incidence of permanent consequences in systemically treated patients, identify possible risk factors  and assess the role of systemic treatment in their prevention
    • To prospectively study the natural course of SS-LCH in patients who initially are not candidates for systemic therapy, with respect to disease progression, reactivations, need for medical interventions, as well as permanent consequences, at any time after diagnosis.

    Eligibility Criteria

    Inclusion criteria include:

    • Diagnosis of Langerhans cell histiocytosis
    • Younger than 18 years old
    • Meets inclusion criteria for the respective stratum

    Exclusion Criteria include:

    • Stratum-dependent

    Study Sites

    St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.

  2. About this study

    Langerhans cell histiocytosis[aa1]  (LCH) is a rare disease that causes too many Langerhans cells (a type of white blood cell) to grow. It is most common in children and young adults. LCH can affect many different parts of the body, including the bones, skin and lungs. It can damage these tissues and organs and also affect the pituitary gland. This gland makes hormones that control many body functions, such as growth.

    Previous clinical trials have improved the treatment and care for children with LCH. However, some patients still do not respond to initial treatment. Others may respond to initial treatment but the disease comes back later. In this study, researchers want to tailor treatment, based on the extent and type of LCH patients have and how they respond to therapy. Participants will be divided into different groups, depending on the level of disease they have. Each group is called a stratum.

    Purpose of this clinical trial

    The main goal of this study is to see how tailored treatments affect LCH in children and adolescents.

    Eligibility overview

    • Diagnosis of Langerhans cell histiocytosis
    • Younger than 18 years old
    • Meets inclusion criteria for the respective stratum
  3. LCH-IV  Quick View
    North American sponsor North American Consortium for Histiocytosis
    International sponsor St. Anna Kinderkrebsforschung, Children's Cancer Research Institute, Vienna, Austria
    Clinicaltrials.gov identifier NCT02205762
    Trial start date July 2014            
    Estimated enrollment 1400 (30 at St. Jude)
    Study type Interventional
    Study phase Phase II/III
    Conditions Langerhans cell histiocytosis
    Ages Up to 18 years old
    Principal investigator Patrick Campbell, MD, PhD (at St. Jude)
    Study sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss LCH-IV
    St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org
     

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.