Histiocytoma

Researchers are evaluating treatment approaches for children newly diagnosed with Langerhans Cell Histiocytosis (LCH), a rare condition affecting various organs. This prospective study focuses on using a protocol that contains cytarabine, aiming to improve outcomes by adjusting treatment intensity and duration. The study divides patients into groups based on disease extent and risk organ involvement, building on previous findings about response rates and survival in children with multisystem LCH. Treatment varies by group: Patients with multisystem disease involving risk organs receive an initial 6-week therapy followed by 16 weeks of consolidation and 26 weeks of maintenance therapy including prednisone, cytarabine, vincristine, and mercaptopurine. Patients with multisystem disease without risk organ involvement get 6 weeks of initial therapy with cytarabine and 46 weeks of continuation therapy without cytarabine. Those with single system or special site involvement receive 6 weeks of initial treatment and 46 weeks of continuation without cytarabine. Patients with single system, unifocal disease receive local therapy followed by observation, with chemotherapy reserved for disease reactivation. Participants will be monitored through various evaluations including response rates at week 6 or 12 for those with risk organ involvement, and reactivation rates up to 5 years for all patients. Overall survival is also tracked for patients with risk organ involvement. The study involves clinical assessments, laboratory tests, and follow-up visits over several years to measure treatment effects and disease progression, with a total participation period extending up to five years.

Researchers are evaluating noninvasive imaging methods to study the appearance of skin and mucosal lesions to improve diagnostic accuracy before a biopsy is needed and to help guide treatment planning. This study involves creating an Image Repository to store these images for clinical practice, teaching, training, and future research. It uses a high-resolution Optical Coherence Tomography (OCT) device called ApolloVueae S100 Image System that provides detailed cross-sectional and en-face images with cellular information. Participants with muco-cutaneous lesions, including normal skin, benign lesions, or neoplastic conditions, identified during routine clinical care will undergo various non-invasive imaging tests. These include dermoscopic imaging, 3-dimensional total body photography, confocal microscopy, OCT imaging, ultrasound, hyperspectral imaging, electrical impedance spectroscopy, and patient self-imaging using mobile phone technology with dermatoscope attachments. Images will be collected of untreated and treated lesions over a period of 7 years. Participants will have their lesions imaged using these non-invasive tools, with images collected and stored in the Image Repository. Assessments include capturing detailed images using specialized devices to evaluate lesion morphology, depth, vascular features, and biochemical information. Researchers will monitor the imaging data to support clinical decisions, teaching, and future research. Participation may involve multiple imaging sessions over time, and safety monitoring includes ensuring no allergic reactions to imaging materials. The study welcomes healthy volunteers and all ages, with informed consent or parental consent and patient assent as applicable.

Researchers are evaluating the use of 3D printed models in planning surgeries to remove tumors that involve bones. This randomized controlled study will compare the effectiveness of using 3D printed models along with imaging to planning surgery using only imaging techniques such as CT or MRI. The goal is to improve surgical outcomes for patients with bone-invading tumors such as sarcoma and osteosarcoma across multiple centers and sites. Participants will be randomly assigned to one of two groups. One group will have their tumor excision planned using standard imaging techniques only, while the other group will have surgery planned with the help of patient-specific 3D printed anatomic models along with imaging. Both groups will undergo tumor removal surgery, with the study lasting about 12 months and including up to 150 subjects. Throughout the study, researchers will measure the time taken for the surgical procedure from incision to closure as the main outcome. They will also monitor blood loss during surgery, any adverse events up to 90 days after surgery, and whether the tumor was completely removed with negative margins. Additional assessments will include how easy the surgical planning was, any changes made to the plan, and the surgeon's satisfaction. Participants will undergo required imaging and surgery, with follow-up to assess safety and outcomes.

Researchers are evaluating the safety, side effects, best dose, and activity of tovorafenib (DAY101) in treating children and young adults with progressive, relapsed, or refractory Langerhans cell histiocytosis (LCH), a disease where too many immature Langerhans cells build up and form tumors in organs like bones, skin, lungs, and pituitary gland. This phase II trial focuses on patients whose disease is growing, spreading, or returning after prior treatment. The study aims to understand how well tovorafenib works and its effects on patients with different genetic mutations related to LCH. Participants receive tovorafenib orally once a week on days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles unless the disease worsens or side effects are unacceptable. Throughout the trial, patients undergo imaging scans such as MUGA or echocardiography and FDG-PET or CT to monitor disease status. Blood and urine samples are collected regularly. Those suspected of having bone marrow or central nervous system involvement will also have bone marrow biopsies, aspirations, and lumbar punctures during the study and follow-up. Patients are involved in regular assessments including scans, laboratory tests, and sample collections to monitor response and safety. Follow-up visits occur 28 days after treatment ends, then at 3, 6, 9, and 12 months, and finally 2 years after completing treatment. The main measures include overall response rate after 2 cycles, event-free survival, progression-free survival, duration of response, and overall survival, with safety monitored continuously throughout the trial.

Researchers are studying adult patients with pulmonary Langerhans cell histiocytosis (PLCH) to understand their long-term outcomes, especially survival rates. This is the first prospective national study using a large registry of PLCH patients in France, followed over many years to identify risk factors affecting their prognosis. The study is observational and aims to provide valuable information on the disease course in adults. Participants include adults aged 18 years or older who have been newly diagnosed with PLCH. Diagnosis is confirmed either by biopsy or through a combination of clinical signs, specific lung imaging patterns on high-resolution CT scans, and ruling out other diseases. Patients receive standard care for PLCH as part of the study. During the study, researchers will monitor overall survival over 20 years as the main outcome. They will also track additional health data including clinical report forms, pulmonary hypertension, occurrence of malignant diseases, involvement beyond the lungs, and yearly disease prevalence. This long-term follow-up helps to understand the disease progression and patient health over time.

Skin cancer cases, including both melanoma and non-melanoma types, have been steadily rising over recent decades. This research investigates new imaging technologies to improve the diagnosis of pigmented and non-pigmented skin tumors without needing invasive biopsies. The study evaluates the use of a high-resolution optical coherence tomography (OCT) scanner, the ApolloVueae S100 Image System, which offers detailed skin imaging at the cellular level and combines advantages of existing imaging methods like confocal microscopy and traditional OCT. The study uses the ApolloVueae S100, a CE-certified device that produces two-dimensional, cross-sectional, and en-face images of the skin in real time. This system employs a special light source and camera to create high-speed, high-resolution images, allowing precise examination of skin lesions. Other imaging devices such as confocal microscopy, Vivascopeae, Vivosightae OCT, and dermoscopy with DermLite FotoXae are also used for comparison on a subset of skin lesions. The system's guiding mechanism helps position the probe accurately for detailed scans during the study. Participants with pigmented or non-pigmented skin lesions scheduled for biopsy or excision will undergo imaging assessments using these devices. Researchers will characterize disease features and evaluate diagnostic accuracy over approximately 1.5 years. Data collected includes OCT images, lesion positions, and clinical assessments. This non-invasive imaging study aims to improve skin tumor evaluation while reducing unnecessary biopsies, with no additional treatments given. Participants' progress and skin lesion images will be monitored and recorded throughout the study period.

Researchers are studying a drug called cobimetinib in children and adults who have Langerhans cell histiocytosis (LCH) or other histiocytic disorders that have returned or do not respond to treatment. These disorders involve immune cells called histiocytes that grow abnormally due to genetic mutations, causing damage to tissues and organs. Some patients with LCH may develop neurodegeneration, which affects brain function. This phase 2 study aims to assess whether cobimetinib, which blocks a protein involved in abnormal cell growth, is safe and effective in treating these conditions, including patients with a specific mutation called BRAF-V600E. The study includes four groups of patients based on age and type of histiocytic disorder. Cobimetinib will be given orally as a tablet or suspension once daily for 21 days followed by 7 days off, making a 28-day treatment cycle. Children under 18 will receive up to 60 mg daily, and adults 18 or older will receive 40 mg daily. Participants will receive up to 12 cycles of treatment, approximately 12 months in total. Participants will be monitored regularly through clinical evaluations, imaging, and laboratory tests to measure overall response rates after 12 months using modified RECIST criteria. Researchers will also assess progression-free survival and record any side effects or adverse events during the study. Safety and effectiveness data will be collected throughout the treatment period to understand how patients respond to cobimetinib. The entire participation time is about one year of treatment and follow-up.

This research aims to improve diagnosis for children with histiocytosis by analyzing the molecular characteristics of tumor tissues and monitoring these markers in circulating DNA. It also evaluates the usefulness and safety of fluorodeoxyglucose (18F-FDG) in PET-CT scans to detect the disease. The study is part of the POLHISTIO project, focusing on better understanding and treating juvenile histiocytosis by linking molecular test results with clinical data and known prognostic factors. Participants receive fluorodeoxyglucose (18F-FDG) as part of PET-CT imaging, with dosing up to a maximum of 6 MGBq/kg but not exceeding 100 MGBq. The study is a low intervention, open-label trial conducted at a single center, including children under 18 years old with confirmed or suspected histiocytosis. Researchers will also develop a cell line from patient samples to study disease mechanisms and drug responses. Throughout the study, children will undergo molecular testing of tumor tissue and blood for circulating DNA markers, along with PET-CT imaging using fluorodeoxyglucose. The study will monitor event-free survival over two years as the main outcome, along with overall survival and detection of molecular relapse. Safety and diagnostic effectiveness of the imaging agent will also be assessed. Participation involves regular clinical evaluations and laboratory tests over the study period, which extends up to two years for outcome tracking.

Researchers are evaluating a combination of two drugs, vemurafenib and cobimetinib, in adults with rare cancers or less common cases of common cancers that have a specific mutation called BRAF V600. This trial is part of the DETERMINE program, which aims to match targeted therapies to rare or molecularly defined cancers. The goal is to see if these drugs, already approved for certain melanoma patients, could be helpful for other cancer types with the same mutation, potentially leading to wider access through the NHS and Cancer Drugs Fund. Participants will receive vemurafenib orally twice daily at a dose of 960 mg throughout 28-day cycles, and cobimetinib orally once daily at 60 mg for 21 days followed by a 7-day break each cycle. Treatment continues until the cancer progresses without benefit, unacceptable side effects occur, or the patient chooses to stop. Before treatment, patients undergo biopsy and blood sample collection. After treatment ends, patients are followed up every three months for two years to monitor health and disease status. Throughout the study, patients will have disease assessments every two cycles (56 days) and at the end of treatment, with less frequent follow-ups after 24 weeks if agreed with the sponsor. Blood samples and quality of life surveys are collected regularly during treatment and follow-up. Researchers will measure tumor response, duration of response, survival times, and adverse reactions to assess the treatments. The whole study participation can last up to five years including treatment and follow-up periods.

This research aims to evaluate the effectiveness and safety of a treatment combining low-dose cytarabine with thalidomide for adults newly diagnosed with Langerhans Cell Histiocytosis (LCH), a rare disease affecting multiple or single systems with multiple lesions. The study focuses on patients who have not received prior systemic treatment and seeks to understand how this treatment impacts event-free survival over a three-year period. Participants will receive cytarabine at 100 mg/m² daily from days 1 to 5 combined with thalidomide 100 mg daily from days 1 to 35, repeated every 35 days for 12 cycles. After this initial phase, participants will continue with thalidomide alone at 100 mg daily from days 1 to 28 every 28 days for an additional 12 cycles, totaling 24 treatment cycles. The study is a multicenter, single-arm trial assessing this combined and maintenance therapy in adults. Throughout the study, participants will be monitored for event-free survival as the primary outcome, along with overall survival, overall response rate, and adverse events up to three years from enrollment. Safety and treatment effects will be carefully tracked, and patient assessments will include clinical evaluations and laboratory tests during treatment and follow-up. The total duration of participation covers the treatment cycles and extends to three years for outcome measurement.