Hemophagocytic LymphohistiocytosesPhase 4NCT05491304
Cytokine Guided Risk Stratification and Treatment in Pediatric Hemophagocytic Lymphohistiocytosis
A Phase 4 study testing Dexamethasone, Etoposide and Ruxolitinib in people with Hemophagocytic Lymphohistiocytoses and Cytokine Storm, run by The Children's Hospital of Zhejiang University School of Medicine at 1 site in China.
Trial summary
Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune-dysregulation characterized by hypercytokinemia, with about 30%-40% of patients suffering death in children. Stratification strategy and individualized treatment is important to improve the survival. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Hemophagocytic Lymphohistiocytoses, Cytokine Storm
- What is being tested?
- Dexamethasone, Etoposide and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2022to 31 Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age from one day to 18 years old；
- 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.
Who cannot join
- treated with steroids or etoposide within 72 hours before diagnosis.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The Children's Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Aimei Ma, bachelor, +8657180070072, zuchiec@163.com
About this study
Official title: Clinical Study on the Treatment of Pediatric Hemophagocytic Lymphohistiocytosis Based on Cytokine Guided Risk Stratification：A Multicenter Randomized Controlled Study
Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune-dysregulation characterized by hypercytokinemia, with about 30%-40% of patients suffering death in children. Stratification strategy and individualized treatment is important to improve the survival. In our recent retrospective study, risk stratification based on IL-10 and IFN-γ levels well distinguished patients with different outcomes. In this multicenter prospective study, we will enroll the newly diagnosed pediatric HLH patients and divide them into low, intermediate and high-risk cytokine groups according to IFN-γ and IL-10 levels. The patients'clinical manifestation and laboratory findings will be further evaluated into severe and non-severe groups. For low/intermediate risk and non-severe patients, steroid or ruxolitinib will be used initially; while those with high risk or severe diseases, DXM+VP16±ruxolitinib will be administered. The treatment strategy could be adjusted after evaluation 48-72 hours later.
Read the detailed description
Background and objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune-dysregulation characterized by hypercytokinemia, with about 30%-40% of patients suffering death in children. Early death is an important issue in HLH treatment, which is greatly caused by hypercytokinemia resulting in multi-organ disfunction and partially due to the treatment toxicities. Thus, stratification strategy and individualized treatment is important to improve the survival. In our recent retrospective study which enrolled 256 pediatric patients, the patients were stratified into low, intermediate and high risk according to their IL-10 and IFN-γ levels. The 8-week mortality for low, intermediate and high-risk patients were 5.4±2.4%, 16.9±3.4% and 48.7±8.0%, and the 5-year OS rate were 82.9±40%, 67.0±4.3% and 51.3±8.0%, respectively. This indicated that IFN-γ and IL-10 are helpful for stratifying HLH patients into different risk groups to receive individualized therapies. However, evidence of cytokine application based on multi-center prospective study is still lacking. The aim of this protocol is to establish a model to early identify the patients with low and high mortality and to guide the precise treatment of pediatric HLH.
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
- Hemophagocytic Lymphohistiocytoses, Cytokine Storm
- Being tested
- Dexamethasone, Etoposide, Ruxolitinib
- Keywords
- Hemophagocytic Lymphohistiocytoses, Cytokine Storm, Ruxolitinib, Interferon-gamma, Interleukin-10, Child, Stratification therapy
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Steroid, Corticosteroid
Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.
EtoposideDrug
Also called VP16
Used in severe group combined with etoposide.
RuxolitinibDrug
Also called JAK1/2 inhibitor
Single drug in non-severe group; combined with etoposide and dexamethasone in severe group.
| Study group | Role | What they receive |
|---|---|---|
| Non-severe DXM group | Experimental | 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. Receives: Drug: Dexamethasone |
| Non-severe Ruxo group | Experimental | Ruxolitinib(Ruxo): body weight (BW)<10kg: 2.5mg Bid; 10-20kg: 5mg Bid; >20kg: 10mg Bid; Orally for 4 weeks. Receives: Drug: Ruxolitinib |
| Severe HLH-94 group | Experimental | 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. Receives: Drug: Dexamethasone; Drug: Etoposide |
| Severe HLH-94 plus ruxolitinib group | Experimental | 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. Receives: Drug: Dexamethasone; Drug: Etoposide; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission (CR)
Complete remission rate in 8th week
Measured: 8th week after the initial of therapy
Overall survival (OS)
Overall survival rate in one year
Measured: One year after enrollment
overall response rate (ORR)
including the proportion of patients achieving CR, PR and HLH improvement
Measured: At the 4th and 8th week of treatment
Mortality
8-week mortality
Measured: At the 8th week of diagnosis
Secondary outcomes (3)
Reactivation rate
The relapse rate of disease
Measured: Any time during the first year after diagnosis
Partial remission (PR)
Partial remission rate in 4th week
Measured: 4th week after the initial of therapy
Rate of Early Death
Death occurred within 2 weeks after diagnosis
Measured: 2nd week after diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2022
- Study start1 Sep 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Hemophagocytic LymphohistiocytosesStudies of the same condition, open and under way.
- More trials run by The Children's Hospital of Zhejiang University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The patients will be divide into different risk groups according to cytokine concentration, clinical manifestation and laboratory findings. 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.
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- The Second Hospital of Anhui Medical University, Union hospital of Fujian Medical University, Children's Hospital of Fudan University, Zunyi Medical College, Hunan Provincial People's Hospital, Tongji Hospital, Children's Hospital of Nanjing Medical University, The Affiliated Hospital of Qingdao University, Qilu Hospital of Shandong University, Shanghai Children's Medical Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Hospital, Shenzhen Children's Hospital, West China Second University Hospital, Children's Hospital of Soochow University, Second Affiliated Hospital of Wenzhou Medical University, Wuhan Children's Hospital, Institute of Hematology & Blood Diseases Hospital, China, The Third Xiangya Hospital of Central South University, First Affiliated Hospital, Sun Yat-Sen University
- Responsible party
- Principal investigator, Xiaojun Xu, The Children's Hospital of Zhejiang University School of Medicine
- Investigators
- Xiaojun Xu, MD, Principal investigator, The Children's Hospital of Zhejiang University School of MedicineYongmin Tang, MD, Principal investigator, The Children's Hospital of Zhejiang University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05491304
- Sponsor's protocol ID
- 2022-IRB-057
- Status last verified
- Oct 2022
- First submitted
- 4 Aug 2022
- Last updated
- 6 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 28935695Xu 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.
PubMed 31506890Tang 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.
PubMed 18673367Xu 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.
PubMed 22226576Xu 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.
PubMed 35296096Wang 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.
PubMed 33559893Zhang 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.
PubMed 35344583Ehl 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.
PubMed 30201097Henter 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.
PubMed 16937360
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on the Treatment of Pediatric Hemophagocytic Lymphohistiocytosis Based on Cytokine Guided Risk Stratification：A Multicenter Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT05491304
- Acronym / sponsor ID
- 2022-IRB-057
- Conditions
- Hemophagocytic Lymphohistiocytoses, Cytokine Storm
- Keywords
- Hemophagocytic Lymphohistiocytoses, Cytokine Storm, Ruxolitinib, Interferon-gamma, Interleukin-10, Child, Stratification therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- The Children's Hospital of Zhejiang University School of MedicineUniversity, hospital or other
- Collaborators
- The Second Hospital of Anhui Medical University, Union hospital of Fujian Medical University, Children's Hospital of Fudan University, Zunyi Medical College, Hunan Provincial People's Hospital, Tongji Hospital, Children's Hospital of Nanjing Medical University, The Affiliated Hospital of Qingdao University, Qilu Hospital of Shandong University, Shanghai Children's Medical Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Hospital, Shenzhen Children's Hospital, West China Second University Hospital, Children's Hospital of Soochow University, Second Affiliated Hospital of Wenzhou Medical University, Wuhan Children's Hospital, Institute of Hematology & Blood Diseases Hospital, China, The Third Xiangya Hospital of Central South University, First Affiliated Hospital, Sun Yat-Sen University
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 8 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune-dysregulation characterized by hypercytokinemia, with about 30%-40% of patients suffering death in children. Stratification strategy and individualized treatment is important to improve the survival. In our recent retrospective study, risk stratification based on IL-10 and IFN-γ levels well distinguished patients with different outcomes. In this multicenter prospective study, we will enroll the newly diagnosed pediatric HLH patients and divide them into low, intermediate and high-risk cytokine groups according to IFN-γ and IL-10 levels. The patients'clinical manifestation and laboratory findings will be further evaluated into severe and non-severe groups. For low/intermediate risk and non-severe patients, steroid or ruxolitinib will be used initially; while those with high risk or severe diseases, DXM+VP16±ruxolitinib will be administered. The treatment strategy could be adjusted after evaluation 48-72 hours later.
Detailed description
Background and objectives: Hemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by immune-dysregulation characterized by hypercytokinemia, with about 30%-40% of patients suffering death in children. Early death is an important issue in HLH treatment, which is greatly caused by hypercytokinemia resulting in multi-organ disfunction and partially due to the treatment toxicities. Thus, stratification strategy and individualized treatment is important to improve the survival. In our recent retrospective study which enrolled 256 pediatric patients, the patients were stratified into low, intermediate and high risk according to their IL-10 and IFN-γ levels. The 8-week mortality for low, intermediate and high-risk patients were 5.4±2.4%, 16.9±3.4% and 48.7±8.0%, and the 5-year OS rate were 82.9±40%, 67.0±4.3% and 51.3±8.0%, respectively. This indicated that IFN-γ and IL-10 are helpful for stratifying HLH patients into different risk groups to receive individualized therapies. However, evidence of cytokine application based on multi-center prospective study is still lacking. The aim of this protocol is to establish a model to early identify the patients with low and high mortality and to guide the precise treatment of pediatric HLH.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The patients will be divide into different risk groups according to cytokine concentration, clinical manifestation and laboratory findings. 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.
| Arm | Type | Receives |
|---|---|---|
| Non-severe DXM group | Experimental | Drug: DexamethasoneDexamethasone (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. |
| Non-severe Ruxo group | Experimental | Drug: RuxolitinibRuxolitinib(Ruxo): body weight (BW)<10kg: 2.5mg Bid; 10-20kg: 5mg Bid; >20kg: 10mg Bid; Orally for 4 weeks. |
| Severe HLH-94 group | Experimental | Drug: Dexamethasone, Drug: EtoposideDXM: 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. |
| Severe HLH-94 plus ruxolitinib group | Experimental | Drug: Dexamethasone, Drug: Etoposide, Drug: RuxolitinibDXM: 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. |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Age from one day to 18 years old；
- 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.
Key exclusion criteria (1 listed)
- treated with steroids or etoposide within 72 hours before diagnosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: Steroid, CorticosteroidSingle drug in non-severe group; combined with etoposide±ruxolitinib in severe group. | Drug | Non-severe DXM group, Severe HLH-94 group, Severe HLH-94 plus ruxolitinib group |
| EtoposideAlso: VP16Used in severe group combined with etoposide. | Drug | Severe HLH-94 group, Severe HLH-94 plus ruxolitinib group |
| RuxolitinibAlso: JAK1/2 inhibitorSingle drug in non-severe group; combined with etoposide and dexamethasone in severe group. | Drug | Non-severe Ruxo group, Severe HLH-94 plus ruxolitinib group |
Primary outcome
Complete remission (CR)
Time frame: 8th week after the initial of therapy
Complete remission rate in 8th week
Overall survival (OS)
Time frame: One year after enrollment
Overall survival rate in one year
overall response rate (ORR)
Time frame: At the 4th and 8th week of treatment
including the proportion of patients achieving CR, PR and HLH improvement
Mortality
Time frame: At the 8th week of diagnosis
8-week mortality
3 secondary outcomes
Reactivation rate
Time frame: Any time during the first year after diagnosis
Partial remission (PR)
Time frame: 4th week after the initial of therapy
Rate of Early Death
Time frame: 2nd week after diagnosis
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2022.
- Background: PubMed 28935695Bergsten 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.
- Background: PubMed 31506890Xu 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.
- Background: PubMed 18673367Tang 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.
- Background: PubMed 22226576Xu 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.
- Background: PubMed 35296096Xu 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.
- Background: PubMed 33559893Wang 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.
- Background: PubMed 35344583Zhang 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.
- Background: PubMed 30201097Ehl 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.
- Background: PubMed 16937360Henter 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaojun Xu, MD principal investigator
The Children's Hospital of Zhejiang University School of Medicine
Yongmin Tang, MD principal investigator
The Children's Hospital of Zhejiang University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dexamethasone, Etoposide and Ruxolitinib in people with Hemophagocytic Lymphohistiocytoses and Cytokine Storm, run by The Children's Hospital of Zhejiang University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaojun Xu, MD (+8657188873617, xuxiaojun@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (CR) (time frame: 8th week after the initial of therapy). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05491304, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2022.