Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis
2 other identifiers
interventional
10
1 country
13
Brief Summary
This study is a multi-site Phase Ib/II, 2-arm non-randomized clinical trial to determine the efficacy and tolerability of a response-adapted regimen combining ruxolitinib, dexamethasone, and etoposide as Frontline therapy for patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH) or as Salvage therapy for patients with relapsed/refractory HLH. Primary Objective
- To determine the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with newly diagnosed HLH. Secondary Objectives
- To describe the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with relapsed/refractory HLH.
- 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
- To estimate the pharmacokinetic (PK) parameters of ruxolitinib, assess covariates of ruxolitinib pharmacokinetics, and test whether the drug's effectiveness is correlated with systemic drug exposure.
- To query specific immunologic biomarkers and determine whether the levels of these biomarkers correlate with disease response and outcome.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2021
Longer than P75 for phase_1
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 2, 2020
CompletedFirst Posted
Study publicly available on registry
September 16, 2020
CompletedStudy Start
First participant enrolled
July 13, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 7, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2026
ExpectedApril 24, 2026
April 1, 2026
4.3 years
September 2, 2020
April 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Complete Response (CR)/Complete Response with Incomplete Hematologic Recovery (CRi)
Will be reported as number and percentage of patients meeting CR/CRi criteria at the end of 8 weeks of therapy
8 weeks
Adverse events (AEs) associated with the ruxolitinib-containing regimen
Cumulative incidence will be estimated by the Kalbfleisch-Prentice method for severe toxicities that lead to morbidity and mortality.
up to 8 weeks
Adverse events (AEs) associated with the ruxolitinib-containing regimen
Cumulative incidence will be estimated by the Kalbfleisch-Prentice method for severe toxicities that lead to morbidity and mortality.
up to 1 year after diagnosis
Secondary Outcomes (6)
Overall Response (CR/CRi plus Partial Response [PR]))
8 weeks
Survival to eight weeks
8 weeks
Survival to allogeneic hematopoietic stem cell transplantation (HSCT) in patients for whom an allogeneic HSCT is planned
up to 1 year
Survival to one year after initiation of the treatment protocol
1 year after initiation of treatment
Survival one year after HSCT
1 year post HSCT
- +1 more secondary outcomes
Study Arms (2)
Frontline Arm
EXPERIMENTALSafety Phase: Patients with newly diagnosed HLH will receive ruxolitinib PO or NGT and dexamethasone, PO or IV. Etoposide IV will be added based on disease response. Expansion Phase: Patients with newly diagnosed HLH treatment will begin with ruxolitinib PO or NGT at the MTD dose. Dexamethasone will be administered PO or IV. Etoposide IV will be added based on disease response.
Salvage Arm
EXPERIMENTALPatients with relapsed/refractory HLH will receive ruxolitinib PO or NGT and dexamethasone PO or IV. Etoposide IV will be added based on disease response.
Interventions
Given orally (PO) or per nasogastric tube (NGT) twice a day for 8 weeks
Given intravenously (IV) or orally (PO) twice a day for 8 weeks
Given intravenously (IV) once a week for 8 weeks
Eligibility Criteria
You may qualify if:
- Patient is ≥6 weeks and ≤22 years of age.
- Patient weighs ≥3 kg.
- Patient is able to take medication PO and/or patient or parent is willing to have NG tube placed if patient is unable to take medications PO.
- Patient has active HLH if:
- Patient has ≥5 of 8 Diagnostic HLH criteria listed below, OR
- Patient has known fHLH (e.g., patient has pathogenic/likely pathogenic germline variant(s) in genes such as PRF1, UNC13D, STX11, STXBP2, LYST, RAB27A, XIAP, SH2D1A, NLCR4) and meets ≥4 of the diagnostic HLH criteria listed below, OR
- Patient has high likelihood of fHLH based on absent perforin, SAP, XIAP expression and meets ≥4 of the Diagnostic HLH Criteria listed below:
- Fever
- Splenomegaly (If present at any point prior to starting study drug)
- Cytopenias affecting ≥2 of 3 cell lineages in the peripheral blood (hemoglobin \<9 g/dL, platelets \<100 × 10\^9/L, ANC \<1000/mm\^3)
- Hypertriglyceridemia (fasting triglycerides ≥265 mg/dL) or hypofibrinogenemia (fibrinogen ≤150 mg/dL)
- Presence of hemophagocytosis in BM or other tissues
- Low or absent NK-cell activity (if present at any point prior to starting study drug) OR decreased CD107a mobilization (if present at any point prior to starting study drug)
- Ferritin ≥500 ng/mL
- Soluble IL-2 receptor (CD25) ≥2400 U/mL
- +21 more criteria
You may not qualify if:
- Patient is \<6 weeks or \>22 years of age.
- Patient weighs \<3 kg.
- Patient has isolated CNS disease.
- Life expectancy is \<2 weeks.
- Patient is likely to require \<4 weeks of therapy (i.e., HSCT is imminent).
- Patients with creatinine clearance (CrCl) \<15 mL/min who are NOT receiving dialysis.
- Patient has evidence of severe organ dysfunction, defined as: Severe liver dysfunction (ALT \>1000 U/L), OR Cardiorespiratory failure requiring any ionotropic support OR extracorporeal life support, OR high frequency oscillatory ventilation, other forms of respiratory support or ventilation are allowed if the patient is not on vasopressors)
- Patient with pre-existing rheumatologic disorder.
- Patient with known active malignancy.
- Patient with previous HSCT, except when HSCT was for treatment of HLH.
- Patient is pregnant or lactating.
- Patients who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with the screening visit through the end of the treatment visit.
- Patient has suspected or known fungal disease.
- Patient is unable to tolerate administration of drugs PO or NG.
- Patient is taking rifampin or St. John's Wort.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- St. Jude Children's Research Hospitallead
- Incyte Corporationcollaborator
- North American Consortium for Histiocytosiscollaborator
- Cures Within Reachcollaborator
Study Sites (13)
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
University of California San Francisco
San Francisco, California, 94158, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
John Hopkins University
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Cohen Children's Medical Center
New Hyde Park, New York, 11040, United States
Levine Children's Hospital
Charlotte, North Carolina, 28203, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75235, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Children's Wisconsin/Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Melissa Hines, MD
St. Jude Children's Research Hospital
- STUDY CHAIR
Kim E. Nichols, MD
St. Jude Children's Research Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 2, 2020
First Posted
September 16, 2020
Study Start
July 13, 2021
Primary Completion
November 7, 2025
Study Completion (Estimated)
August 1, 2026
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available at the time of article publication.
- Access Criteria
- Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.