View clinical trials related to Histiocytosis, Langerhans-Cell.
Filter by: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.
The long-term goal is to define the mechanisms of pathogenesis underlying Langerhans cell histiocytosis (LCH). The overall objectives of the current study are to characterize the role of SMAD6 inherited genetic variation on LCH susceptibility and identify germline genomic regions associated with LCH somatic mutations. Building from preliminary data, the central hypotheses are: (1) causal genetic variants in SMAD6 underlie susceptibility to LCH, and (2) differences in LCH-related somatic activating mutations by race/ethnicity are related to Amerindian (i.e., Native American) genetic ancestry. The Central hypothesis will be tested by pursuing the specific aims.
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Langerhans cell histiocytosis (LCH) is a disease caused by clonal expansion, proliferation, and dissemination of cells that are phenotypically close to Langerhans cells in different tissues and organs. The clinical presentation of LCH varies greatly from one solid bone tumor to multisystem lesion that involves liver, spleen and bone marrow. The basis of LCH is the clonal proliferation of the pathological cells. These cells express CD1a and CD207 markers on their surface and originate from myeloid progenitors. The main event in life circle of these cells is the MEK-ERK cascade mutation. The most common mutation is the substitution of valine for glutamic acid in position 600 of BRAF gene. The influence of this mutation was confirmed by G.Badalyan-Very et al. in 2010. About 64% of all LCH are caused by clonal proliferation due to BRAF V600E mutation. Despite generally good results of therapy of monosystemic LCH, the treatment of LCH with risk organs lesion is still a challenge: 5-years survival is as low as 40-50%. Combination of cytarabine and 2-chlorodeoxyadenosine was supposed to improve the results, but the cost was a very high toxicity, that limits the application of the regimen in patients with severe infections. Currently, there is a lot of information on BRAF V600E inhibitors in patients with LCH and other histiocytic disorders. Most of them report the dramatic efficacy of BRAF V600E inhibitors but after quick effect patients usually burden minimal disease activity ("plateau" effect). However, discontinuation of the therapy results in quick disease reactivation. Considering this a trial that combines targeted therapy (vemurafenib) and low-dose chemotherapy (cytarabine and 2-chlorodeoxyadenosine) in order to achieve complete response with manageable toxicity is proposed.
This phase II Pediatric MATCH trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back (recurrent) or does not respond to treatment (refractory) and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
This Pediatric MATCH screening and multi-sub-study phase II trial studies how well treatment that is directed by genetic testing works in pediatric patients with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic changes or abnormalities (mutations) may benefit more from treatment which targets their tumor's particular genetic mutation, and may help doctors plan better treatment for patients with solid tumors or non-Hodgkin lymphomas.
Very recent studies indicate that a high percentage of HCL, about 50%, have mutations in the B-RAF oncogene. The development of ultrasensitive methodologies capable of identifying these mutations in bronchoalveolar lavage will represent a significant advance in the diagnosis and treatment of these patients. An undetermined percentage of HCL does not present mutations in B-RAF. Consequently, the deep genetic analysis, through the use of techniques of massive sequencing, can favor the identification of new alterations that contribute to the development of the disease. We hypothesized that patients with HCL may present a different inflammatory state to healthy subjects or smokers, allowing us to identify new biomarkers.
Langerhans Cell Histiocytosis (LCH) is a type of cancer that can damage tissue or cause lesions to form in one or more places in the body. Langerhans cell histiocytosis (LCH) is a cancer that begins in LCH cells (a type of dendritic cell which fights infection). Sometimes there are mutations (changes) in LCH cells as they form. These include mutations of the BRAF gene. These changes may make the LCH cells grow and multiply quickly. This causes LCH cells to build up in certain parts of the body, where they can damage tissue or form lesions. For most patients with LCH, standard-of-care vinblastine/prednisone are used as front-line therapy while cytarabine therapy has been used as therapy for patients who develop recurrence. No alternate treatment strategy has been developed for frontline therapy in LCH. The purpose of this research study is to compare previously used vinblastine/prednisone to single therapy with cytarabine for LCH. We will evaluate the utility of an imaging study called a positron emission tomography (PET) scan to more accurately assess areas of LCH involvement not otherwise seen in other imaging studies as well as response to therapy. We also want to identify if genetic and other biomarkers (special proteins in patient's blood and in patient's cancer) relate to the response of patients LCH to study treatment.
This study gathers health information for the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.
The LCH-IV is an international, multicenter, prospective clinical study for pediatric Langerhans Cell Histiocytosis LCH (age < 18 years).