Cytokine Guided Risk Stratification and Treatment in Pediatric Hemophagocytic Lymphohistiocytosis
NCT ID: NCT05491304
Last Updated: 2022-10-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE4
400 participants
INTERVENTIONAL
2022-09-01
2025-12-31
Brief Summary
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Detailed Description
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Methods and protocol design: A multicenter prospective study in Asian countries is to be launched for children with HLH. The inclusion criterion is newly diagnosed pediatric HLH patients who has not received steroids or etoposide when enrollment. In this study, the patients are identified as low, intermediate and high-risk cytokine groups according to their cytokine levels: (1) low-risk: IFN-γ\<3700pg/mL and IL-10\<200pg/mL; (2) intermediate-risk: IFN-γ\<3700pg/mL and IL-10≥200pg/mL; (3) high-risk: IFN-γ≥3700pg/mL. The patients' clinical manifestation and laboratory findings were evaluated as well and those fulfill either one of the following criteria were considered as "severe": (1) present ≥2 out of 3 ⅰ, albumin\<26.0 g/L; ⅱ, direct bilirubin\>55.0μmol/L; ⅲ, fibrinogen\<0.75g/L. (2) CNS involvement, shock, mechanical ventilation, renal failure.
Based on the cytokine risk and disease severity, different intensity of treatment will be started. For low/intermediate risk and not severe patients, steroid or ruxolitinib will be used initially; while those with high risk or "severe" disease, DXM+VP16±ruxolitinib will be administered. The treatment strategy could be adjusted after evaluation 48-72 hours later based on treatment respose and cytokine levels. A total of 400 pediatric patients under 18 years old are to be recruited. The primary end-point of the study is the 8-week responsive rates and mortality, and one-year overall survival.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Non-severe DXM group
Dexamethasone (DXM): week1-2: 10 mg/m2.d, week 3-4: 5 mg/m2.d, week5-6: 2.5 mg/m2.d, week7: 1.25 mg/m2.d, week8: tapering.
Dexamethasone
Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.
Non-severe Ruxo group
Ruxolitinib(Ruxo): body weight (BW)\<10kg: 2.5mg Bid; 10-20kg: 5mg Bid; \>20kg: 10mg Bid; Orally for 4 weeks.
Ruxolitinib
Single drug in non-severe group; combined with etoposide and dexamethasone in severe group.
Severe HLH-94 group
DXM: week1-2: 10 mg/m2.d, week 3-4: 5 mg/m2.d, week5-6: 2.5 mg/m2.d, week7: 1.25 mg/m2.d, week8: tapering.
Etoposide (VP16): 100-150mg/m2 twice in the first two weeks, and once every week to week 8.
Dexamethasone
Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.
Etoposide
Used in severe group combined with etoposide.
Severe HLH-94 plus ruxolitinib group
DXM: week1-2: 10 mg/m2.d, week 3-4: 5 mg/m2.d, week5-6: 2.5 mg/m2.d, week7: 1.25 mg/m2.d, week8: tapering.
Etoposide (VP16): 100-150mg/m2 twice in the first two weeks, and once every week to week 8.
Ruxolitinib(Ruxo): body weight (BW)\<10kg: 2.5mg Bid; 10-20kg: 5mg Bid; \>20kg: 10mg Bid; Orally for 4 weeks.
Dexamethasone
Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.
Etoposide
Used in severe group combined with etoposide.
Ruxolitinib
Single drug in non-severe group; combined with etoposide and dexamethasone in severe group.
Interventions
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Dexamethasone
Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.
Etoposide
Used in severe group combined with etoposide.
Ruxolitinib
Single drug in non-severe group; combined with etoposide and dexamethasone in severe group.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Newly diagnosed HLH, fulfilling the HLH criteria;
* To observed the early diagnosis role of cytokines, patients who is suspected to be HLH and fulfill 3 out of 8 criteria can be pre-enrolled.
Exclusion Criteria
1 Day
18 Years
ALL
No
Sponsors
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The Second Hospital of Anhui Medical University
OTHER
Union hospital of Fujian Medical University
OTHER
Children's Hospital of Fudan University
OTHER
Zunyi Medical College
OTHER
Hunan Provincial People's Hospital
OTHER
Tongji Hospital
OTHER
Children's Hospital of Nanjing Medical University
OTHER
The Affiliated Hospital of Qingdao University
OTHER
Qilu Hospital of Shandong University
OTHER
Shanghai Children's Medical Center
OTHER
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
OTHER
Shanghai Children's Hospital
OTHER
Shenzhen Children's Hospital
OTHER_GOV
West China Second University Hospital
OTHER
Children's Hospital of Soochow University
OTHER
Second Affiliated Hospital of Wenzhou Medical University
OTHER
Wuhan Children's Hospital
OTHER
Institute of Hematology & Blood Diseases Hospital, China
OTHER
The Third Xiangya Hospital of Central South University
OTHER
First Affiliated Hospital, Sun Yat-Sen University
OTHER
The Children's Hospital of Zhejiang University School of Medicine
OTHER
Responsible Party
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Xiaojun Xu
chief physician
Principal Investigators
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Xiaojun Xu, MD
Role: PRINCIPAL_INVESTIGATOR
The Children's Hospital of Zhejiang University School of Medicine
Yongmin Tang, MD
Role: PRINCIPAL_INVESTIGATOR
The Children's Hospital of Zhejiang University School of Medicine
Locations
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The Children's Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Countries
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Central Contacts
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Facility Contacts
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References
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Bergsten E, Horne A, Arico M, Astigarraga I, Egeler RM, Filipovich AH, Ishii E, Janka G, Ladisch S, Lehmberg K, McClain KL, Minkov M, Montgomery S, Nanduri V, Rosso D, Henter JI. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017 Dec 21;130(25):2728-2738. doi: 10.1182/blood-2017-06-788349. Epub 2017 Sep 21.
Xu XJ, Tang YM. Dilemmas in diagnosis and management of hemophagocytic lymphohistiocytosis in children. World J Pediatr. 2020 Aug;16(4):333-340. doi: 10.1007/s12519-019-00299-3. Epub 2019 Sep 10.
Tang Y, Xu X, Song H, Yang S, Shi S, Wei J, Pan B, Zhao F, Liao C, Luo C. Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome. Br J Haematol. 2008 Oct;143(1):84-91. doi: 10.1111/j.1365-2141.2008.07298.x. Epub 2008 Jul 31.
Xu XJ, Tang YM, Song H, Yang SL, Xu WQ, Zhao N, Shi SW, Shen HP, Mao JQ, Zhang LY, Pan BH. Diagnostic accuracy of a specific cytokine pattern in hemophagocytic lymphohistiocytosis in children. J Pediatr. 2012 Jun;160(6):984-90.e1. doi: 10.1016/j.jpeds.2011.11.046. Epub 2012 Jan 9.
Xu XJ, Luo ZB, Song H, Xu WQ, Henter JI, Zhao N, Wu MH, Tang YM. Simple Evaluation of Clinical Situation and Subtypes of Pediatric Hemophagocytic Lymphohistiocytosis by Cytokine Patterns. Front Immunol. 2022 Feb 28;13:850443. doi: 10.3389/fimmu.2022.850443. eCollection 2022.
Wang J, Zhang R, Wu X, Li F, Yang H, Liu L, Guo H, Zhang X, Mai H, Li H, Wang Z. Ruxolitinib-combined doxorubicin-etoposide-methylprednisolone regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis: a single-arm, multicentre, phase 2 trial. Br J Haematol. 2021 May;193(4):761-768. doi: 10.1111/bjh.17331. Epub 2021 Feb 9.
Zhang Q, Zhao YZ, Ma HH, Wang D, Cui L, Li WJ, Wei A, Wang CJ, Wang TY, Li ZG, Zhang R. A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis. Blood. 2022 Jun 16;139(24):3493-3504. doi: 10.1182/blood.2021014860.
Ehl S, Astigarraga I, von Bahr Greenwood T, Hines M, Horne A, Ishii E, Janka G, Jordan MB, La Rosee P, Lehmberg K, Machowicz R, Nichols KE, Sieni E, Wang Z, Henter JI. Recommendations for the Use of Etoposide-Based Therapy and Bone Marrow Transplantation for the Treatment of HLH: Consensus Statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1508-1517. doi: 10.1016/j.jaip.2018.05.031. Epub 2018 Jul 4.
Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007 Feb;48(2):124-31. doi: 10.1002/pbc.21039.
Other Identifiers
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2022-IRB-057
Identifier Type: -
Identifier Source: org_study_id
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