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

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.

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