This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.

开始日期2024-03-28

申办/合作机构

National Cancer Institute

NCT05477446 / Not yet recruiting临床1期IIT

Safety and Efficacy of CD207 Targeted CAR-T Cell Therapy in Patients With Relapsed and Refractory (R/R) Langerhans Cell Histiocytosis

This is a single-arm study to evaluate the efficacy and safety of CD207 targeted CAR-T cell therapy in relapsed and refractory langerhans cell histiocytosis.

开始日期2022-10-01

申办/合作机构

北京友谊医院

[+1]

ChiCTR2200060467 / Suspended临床1期IIT

Clinical study of the safety and efficacy of chimeric antigen receptor gene-modified T cells targeting CD207 in the treatment of relapsed/refractory Langerhans histiocytosis

开始日期2022-06-01

申办/合作机构-

100 项与难治性朗格汉斯细胞组织细胞增生症相关的临床结果

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100 项与难治性朗格汉斯细胞组织细胞增生症相关的转化医学

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0 项与难治性朗格汉斯细胞组织细胞增生症相关的专利（医药）

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项与难治性朗格汉斯细胞组织细胞增生症相关的文献（医药）

2024-05-01·British Journal of Haematology

Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis

Article

作者: Gulati, Nitya ; Scull, Brooks ; Pillai, Pallavi M. ; Neff, Philip ; Dietz, Matthew S. ; Walkovich, Kelly ; Schiff, Deborah E. ; McClain, Kenneth L. ; Fleishmann, Ryan ; Parekh, Deevyashali ; Allen, Carl E. ; Sisk, Bryan A. ; Trobaugh‐Lotrario, Angela D. ; Intzes, Stefanos ; Batajoo, Akanksha ; Lin, Howard ; Goldman, Stanton C. ; Imran, Hamayun ; Hogarty, Michael D. ; Karri, Vivekanudeep ; Kopp, Lisa M. ; Eckstein, Olive S. ; Stanton, Whitney ; Ahmed, Asra Z. ; Kim, Jenny M. ; Agrusa, Jennifer E. ; El‐Mallawany, Nader ; Levy, Carolyn Fein ; Prudowsky, Zachary D. ; Peckham‐Gregory, Erin ; Chu, Roland

SummaryOver 50% of patients with systemic LCH are not cured with front‐line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long‐term efficacy, late toxicities, relative cost and patient‐reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

2024-05-01·British Journal of Haematology

Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis

Article

作者: Batajoo, Akanksha ; Eckstein, Olive ; Velazquez, Jessica ; Lin, Howard ; Saha, Anikit ; Karri, Vivekanudeep ; Woods‐Swafford, Wendy ; McClain, Kenneth L. ; Allen, Carl E. ; Agrusa, Jennifer ; Boyd, Jaime ; Parekh, Deevyashali ; Stanton, Whitney ; Gulati, Nitya ; Schwartz, Jeffrey ; Abhyankar, Harshal ; El‐Mallawany, Nader K.

SummaryOptimal therapeutic approaches for advanced Langerhans cell histiocytosis (LCH) are not known. We assessed the safety and efficacy of combined chemotherapy with MAPK pathway inhibition in 10 patients with refractory systemic disease and/or LCH‐associated neurodegeneration. Overall response rate was 9/10 (90%) for the entire cohort: 5/5 (100%) for patients with systemic disease and 6/7 (86%) for patients with central nervous system disease. BRAFV600E+ peripheral blood fraction decreased in 5/6 (83%). Toxicities included fever, skin rash, myalgias, neuropathy, cytopenias and hypocalcaemia. Prospective trials are required to optimize combination strategies, determine potential to achieve cure and compare outcomes to chemotherapy or MAPK inhibitor monotherapy.

2024-05-01·Asian Pacific Journal of Cancer Prevention

Nationwide Study of Factors Impacting Survival Outcome and Consequences in Children with Reactivation/Refractory Langerhans Cell Histiocytosis

Article

作者: Komvilaisak, Patcharee ; Sathitsamitphong, Lalita ; Sanpakit, Kleebsabai ; Chainansamit, Su-On ; Seksarn, Panya ; Traivaree, Chanchai ; Suwannaying, Kunanya ; Buaboonnam, Jassada ; Monsereenusorn, Chalinee ; Pakakasama, Samart ; Techavichit, Piti ; Anurathapan, Usanarat ; Charoenkwan, Pimlak

BACKGROUNDDisease reactivation/refractory remains a major challenge in managing Langerhans cell histiocytosis (LCH). Outcomes and late sequelae should be explored.METHODSA multi-institutional retrospective study was conducted to describe clinical characteristics, predictive factors, outcomes and late sequelae of pediatric reactivation/refractory LCH in Thailand.RESULTSIn all, 47 patients were studied, 25 (53.2%) patients had disease reactivation and 22 (46.8%) patients had refractory LCH. The median reactivation and refractory time were 1.59 and 0.33 years from diagnosis, respectively (p <0.001). The most common site of reactivation/refractory was the bone (n = 26, 55%), and 20 (42.6%) patients developed late sequelae. The 5-year overall survival (OS) was 76.1%. Patients with reactivation and refractory LCH performed similarly in 5-year OS (88% vs. 63%, p = 0.055). Prognostic factors associated with mortality were liver, spleen, hematopoietic system and lung reactivation (p <0.05). Lung reactivation was the only independent risk factor associated with the survival outcome (p = 0.002).CONCLUSIONSThe outcomes of pediatric patients between reactivation and refractory LCH in Thailand were similarly desirable and mortality was minimal although late sequelae may evolve. Pulmonary reactivation/refractory was an independent risk factor associated with survival.