Cytokine Guided Risk Stratification and Treatment in Pediatric Hemophagocytic Lymphohistiocytosis

Sponsor
The Children's Hospital of Zhejiang University School of Medicine
Study ID
NCT05491304
Phase
PHASE4
Status
Unknown

Conditions

  • Cytokine Storm
  • Hemophagocytic Lymphohistiocytoses

Eligibility Criteria

Sex
ALL
Age
1 Day - 18 Years
Healthy Volunteers
Not accepted

Interventions

  • Dexamethasone — DRUG
    Single drug in non-severe group; combined with etoposide±ruxolitinib in severe group.
  • Etoposide — DRUG
    Used in severe group combined with etoposide.
  • Ruxolitinib — DRUG
    Single drug in non-severe group; combined with etoposide and dexamethasone in severe group.

Study Details

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.

Key Dates

Start date
Sep 1, 2022
Status verified
Oct 2022
Primary completion
Dec 31, 2024
Completion
Dec 31, 2025

Study Design

Enrollment
400 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Experimental: Non-severe Ruxo group
    Ruxolitinib(Ruxo): body weight (BW)\<10kg: 2.5mg Bid; 10-20kg: 5mg Bid; \>20kg: 10mg Bid; Orally for 4 weeks.
  • Experimental: 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.
  • Experimental: 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.

Primary Outcome Measure

Complete remission (CR) [ Time Frame: 8th week after the initial of therapy ]

Central Contacts

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