Study Background

HLH is a syndromic disorder characterized by overwhelming immune activation and severe hypercytokinemia.  HLH has historically been very difficult to treat and is fatal in up to 90% of cases without therapy.  Great improvements in survival have been made with the introduction of etoposide-based regimens, but overall survival remains suboptimal at ~ 65%.  In addition, etoposide-based regimes are associated with significant toxicities including bone marrow suppression, infection and secondary malignancy.  Due to the continued high mortality and the morbidities associated with current HLH regimens, there is a pressing need for the development of novel therapies to improve the outcomes for patients with HLH.

Recent publications have shown promising evidence for efficacy on the Janus kinase inhibitor ruxolitinib in treatment of HLH.  This study is designed to test the safety and efficacy of combination therapy with ruxolitinib and dexamethasone with addition of etoposide if needed for the treatment of newly diagnosed and refractory HLH.

Primary Objectives 

The primary objective of this study is to determine ​the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with newly diagnosed HLH.                      

Secondary Objectives

  1.  To describe the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with relapsed/refractory HLH.
  2. To describe the overall response and outcome for patients with newly diagnosed or relapsed/refractory HLH who are treated with this response-adapted ruxolitinib-containing regimen.

Exploratory Objectives

  1. To evaluate the pharmacokinetic (PK) parameters of ruxolitinib, access covariates of ruxolitinib pharmacokinetics, and test whether the drug's effectiveness is correlated with systemic drug exposure
  2. To query specific immunologic biomarkers and determine whether the levels of these biomarkers correlate with disease response and outcome.

Site Selection 

A limited number of centers have been selected to participate in the study during the initial site selection process.  Selected sites have been notified by the NACHO Operations Center. ​

Study Team

Clinical Coordinating Center
St. Jude Children's Research Hospital, Memphis, TN
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Study Chair
Melissa Hines, MD
St. Jude Children's Research Hospital, Memphis, TN

Co Chair
Kim Nichols, MD
St. Jude Children's Research Hospital, Memphis, TN

Operations & ​Data Coordinating Center
NACHO Operations Center housed at ​
​St. Jude Children's Research Hospital, Memphis TN 
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Study Manager 
Kristen Ryan, RN, BSN, CCRP
NACHO Operations Center

Project Coordinator 
Sara Grace Clyburn, CCRP 
NACHO Operations Center

ClinicalTrials.gov

View more information about this study on ClinicalTrials.gov Study NCT04551131.