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Ruxolitinib with De-Intensified HLH-94 for Hemophagocytic Lymphohistiocytosis (HLH)

This study is testing a new way to treat Hemophagocytic Lymphohistiocytosis (HLH), a condition where your immune system is overactive and causes damage. It combines ruxolitinib, a drug that blocks signals causing inflammation, with a reduced dose of the standard HLH-94 treatment (dexamethasone and etoposide). The study aims to see how well this combination works in newly diagnosed adults with HLH. To join, you must be 18 or older and meet specific diagnostic criteria for active HLH. The main goal is to see how many participants respond to the treatment within 4 weeks. The study plans to enroll 54 participants, but its current status is unclear.

Study design
This is an interventional study, meaning participants will receive specific treatments. It plans to enroll 54 adult participants.
What's involved
You would receive ruxolitinib orally, and etoposide and dexamethasone either intravenously or orally. You would also have abdominal ultrasounds or MRIs, and bone marrow and lymph node biopsies during screening and as needed.
Compensation
Not stated in the trial record.
Follow-up
The primary response to treatment will be measured at 4 weeks. Other outcomes like progression-free survival and overall survival will also be evaluated.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06160791

Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH)

Recruiting
PHASE2Ages 18+InterventionalTreatment
Jerry Lee, MD, MSc, MPhil
~54 participants
Updated 2026-07-22 on ClinicalTrials.gov
What's tested:RuxolitinibEtoposideDexamethasoneNon-interventional ImagingResearch BiopsyBiospecimen Collection

At a glance

Recruiting sites
3 of 4 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall response rate (ORR)
Measured over 4 weeks

Conditions

Hemophagocytic Lymphohistiocytoses

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NCT06160791

Where you'd take part

This study runs at 4 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • University of California Davis Comprehensive Cancer Center

    Sacramento, Californiastudy coordinator listed

    Recruiting

  • University of California, Irvine

    Irvine, Californiastudy coordinator listed

    Recruiting

  • University of California, San Diego

    San Diego, Californiastudy coordinator listed

    Not yet recruiting

  • University of California, San Francisco

    San Francisco, Californiastudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Jerry Lee, MD · PRINCIPAL_INVESTIGATOR · University of California, San Francisco

Who to contact

UCSF Hematopoietic Malignancies Clinical Trial Recruitment
[email protected]
877-827-3222
Email the study team

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Eligibility criteria

Inclusion

Ability to understand and the willingness to sign a written informed consent document.
Males and females, 18 years of age or older at the time of enrollment.
Participants must have active HLH and meet \>= 5 of 8 of the HLH-2004 diagnostic criteria, or have familial/primary HLH with pathogenic/likely pathogenic germline variant(s) in genes known to cause HLH (e.g., PRF1, UNC13D, Syntaxin 11 (STX11), Syntaxin-binding protein 2 (STXBP2), RAB27A, SH2 domain-containing protein 1A (SH2D1A), baculovirus inhibitor of apoptosis repeat containing protein 4 (BIRC4), Lysosomal trafficking regulator (LYST), interleukin-2-inducible T-cell kinase (ITK), SLC7A7, X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN), Hermansky-Pudlak syndrome (HPS), NLR family CARD domain-containing protein 4 (NLCR4) or other immune regulatory genes.
Fever \>= 38.5 degrees Celsius (C) (or \>= 38 degrees C if acetaminophen given in prior 6 hours).
Splenomegaly.
Peripheral cytopenias involving \>= 2 of 3 cell lines (absolute neutrophil count \< 1000/uL; hemoglobin \< 9 g/dL; platelets \< 100,000/uL).
Hypertriglyceridemia (fasting triglycerides \>= 265 mg/dL) or Hypofibrinogenemia (fibrinogen =\< 150 g/dL).
Hemophagocytosis on tissue biopsy, such as in the bone marrow, spleen, lymph node, or liver.
Low/absent natural killer (NK)-cell activity/perforin and/or decreased CD107a mobilization.
Ferritin \>= 500 ug/L.
Soluble IL-2 receptor (sCD25) \> 2400 U/mL or two standard deviations above age-adjusted laboratory-specific norms.
The effects of ruxolitinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation and for two months after last administration of study treatment.
Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and two months after last administration of study treatment.

Exclusion

Participant is receiving or received any other investigational agent within 1 week of the first dose of treatment.
Females who are pregnant or breastfeeding. Female participants of child-bearing potential must have a negative pregnancy test within 7 days of treatment and lactating females must discontinue breast feeding during treatment and until two weeks after the final dose of ruxolitinib.
Males who expect to conceive children, and/or who decline highly effective methods of contraception during the entire duration of the study.
Patient cannot take medications orally or via a nasogastric/orogastric tube.
Poor life expectancy \< 2 weeks.
Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 6 months, New York Heart Association class III or IV. congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure \> 170/100 mmHg) unless approved by the sponsor- investigator.
Estimated creatine clearance (CrCl) \< 15 mL/min while not on dialysis.
Known (biopsy-confirmed) liver cirrhosis or suspected cirrhosis with a Model for End- Stage Liver Disease (MELD) score of \> 20, or aspartate aminotransferase (AST) or alanine transaminase (ALT) values \> 1000 not expected to improve with HLH therapy.
Severe organ dysfunction, such as cardiorespiratory failure requiring inotropic medications or extracorporeal life support. Respiratory support including intubation/ventilation is allowed.
Newly diagnosed acute and clinically active tuberculosis, hepatitis B, and/or hepatitis C.
Patients with active human immunodeficiency virus (HIV) are not excluded from this study but must be on antiretrovirals.
Patients with hepatitis B or C viremia can be on study if the hepatitis is not considered clinically active and/or if it is chronic. These patients should be discussed with the principal investigator.
Individuals with a prior malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Individuals with chimeric antigen receptor (CAR)-T-associated HLH.
No prior HLH-directed therapy except corticosteroids for \< 2 consecutive weeks and anakinra.
Adjunctive approaches such as rituximab for Epstein-Barr virus (EBV) viremia or IVIG for viral infection are permitted.
Emapalumab, alemtuzumab, anti-thymocyte globulin (ATG), tocilizumab, siltuximab, or prior ruxolitinib are NOT permitted. Cyclosporine and tacrolimus are not permitted in the initial induction period.
Hypersensitivity to ruxolitinib or any of its excipients

What this trial measures

  • Overall response rate (ORR)4 weeks

    The proportion of responder (complete response (CR), complete response with incomplete hematologic recovery, or partial response (PR)) or non-responder at the end of induction using a physician developed response criteria will be reported. Those with non-malignant HLH (nmHLH) will be assessed for response, defined as complete response (CR) + partial response (PR) at 4 weeks. Participants diagnosed with a malignant trigger are recommended to undergo cancer-directed therapy once acute hypercytokinemia improves. The primary endpoint for malignant HLH (mHLH) is achievement of PR or better and initiation of cancer-directed therapy (non-HLH specific therapy) by 4 weeks.