ClinicalTrials.gov record NCT06160791
Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH)
Frontline Ruxolitinib With De-Intensified HLH-94 for Adult Hemophagocytic Lymphohistiocytosis (HLH): A Multicenter, Single-Arm Phase 2 Study
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This single-arm Phase 2 trial tests ruxolitinib given with a reduced-intensity HLH-94 induction (dexamethasone and etoposide) in newly diagnosed adults with hemophagocytic lymphohistiocytosis (HLH). Treatment includes an induction period with ruxolitinib, steroids, and etoposide, followed by continuing ruxolitinib for up to six months if tolerated. The study measures response at 4 weeks and tracks safety, survival measures, and immune and laboratory markers during follow-up.
What it is studying. The study is evaluating the effects of adding ruxolitinib to a de-intensified HLH-94 induction regimen and continuing ruxolitinib thereafter on disease response, safety, and clinical outcomes in adults newly diagnosed with HLH.
What the researchers hope to learn. Primary goal: evaluate the efficacy (response at end of induction) of ruxolitinib combined with de-intensified HLH-94 in adult HLH. Secondary goals: describe toxicities, measure best response, time to and duration of response, progression-free and overall survival, timing of cancer diagnosis and cancer-directed therapy for malignancy-associated HLH, and patterns of adjunctive HLH therapies. Exploratory goals: study T cell subsets, activated CD8+ T cells, cytokine profiles, and relationships between labs/cytokines and treatment response.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
This phase II trial tests the effects of ruxolitinib in combination with a de-intensified HLH-94 drug regimen has on patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), a disorder caused by dysregulated immune responses (that is, immune responses that are too strong and cause inflammatory damage to normal tissues). The therapy used for HLH decreases the activity of the immune system. Ruxolitinib is a type of drug called a kinase inhibitor. It works by blocking the signals that cause inflammatory cells to multiply. De-intensified HLH-94 is a treatment regimen that includes 4 weeks of dexamethasone with the dose being decreased each week, and up to 4 weeks of etoposide. This combination is commonly used to treat HLH. Dexamethasone is a steroid medication that works by fighting inflammation. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill cancer cells and is used to kill the types of white blood cells in HLH that are attacking the body. Giving ruxolitinib in combination with a de-intensified HLH-94 drug regimen may reduce toxic exposure to therapy while maintaining efficacy in patients with HLH.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Ruxolitinib
- Etoposide
- Dexamethasone
- Procedure
- Non-interventional Imaging
- Research Biopsy
- Biospecimen Collection
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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 criteria
- 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.
- Vasopressors are allowed if not required other than low dose vasoconstrictors to compensate the effects of sedation.
- 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
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
PRIMARY OBJECTIVE: I. To evaluate the efficacy of ruxolitinib with de-intensified HLH-94 (dHLH-94; 4 weeks of dexamethasone and etoposide) for newly diagnosed adults with HLH. SECONDARY OBJECTIVES: I. To describe the toxicities of ruxolitinib in combination with de-intensified HLH-94 for the treatment of adult HLH. II. To evaluate best response, time to best response, and duration of response stratified by mHLH and nmHLH. III. To evaluate the progression-free survival (PFS) of using ruxolitinib in combination with dHLH-94 for the treatment of adult HLH, stratified by malignancy-associated hemophagocytic lymphohistiocytosis (mHLH) and non-malignancy-associated hemophagocytic lymphohistiocytosis (nmHLH). IV. To evaluate the overall survival (OS) when using ruxolitinib in combination with de-intensified HLH-94 for the treatment of adult HLH, stratified by mHLH and nmHLH. V. To evaluate the time to cancer diagnosis for HLH, among those ultimately diagnosed with mHLH. VI. To evaluate the time to cancer-directed therapy from the diagnosis of mHLH. VII. To describe the practice patterns of adjunctive therapies (i.e., rituximab, intravenous immunoglobulin therapy (IVIG), anakinra) for HLH. EXPLORATORY OBJECTIVES: I. To identify T cell subsets that are differentially increased in adult HLH (comparing mHLH and nmHLH). II. To evaluate the association of CD8+ T cell subsets expressing CD4dim/CD38+/HLA-DR+ ("activated T cells") with clinical deterioration. III. To evaluate the relationship between the peripheral blood cytokine microenvironment (e.g., Interleukin 1b (IL-1b), Interleukin 2 (IL-2), Interleukin 6 (IL-6), Interleukin 10 (IL-10), Interleukin 18 (IL-18), Interferon gamma (IFN-gamma), Tumor Necrosis Factor alpha (TNF alpha), laboratory parameters (ferritin, blood counts, liver function, fibrinogen), and response to ruxolitinib. OUTLINE: During induction therapy, participants receive ruxolitinib plus de-intensified HLH-94 induction with dexamethasone and etoposide and then based on response, another 2 weeks of treatment will be given in the absence of disease progression or unacceptable toxicity. After induction therapy, participants receive continuation therapy with ruxolitinib for a total of up to 6 months after first administration of study drug in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days and then at 3, 6, and 12 months
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive oral ruxolitinib twice daily together with a de‑intensified HLH‑94 induction (dexamethasone for 4 weeks by mouth or IV and etoposide IV twice weekly for 2 weeks, then response‑guided once weekly for up to 2 more weeks). After induction, participants continue ruxolitinib in 28‑day cycles for up to about 6 months if there is no disease progression or unacceptable toxicity. Study procedures include bone marrow and lymph node biopsies (at screening and as needed), abdominal ultrasound and/or MRI, and repeated blood sample collection for research. After finishing study treatment there are follow-up visits at about 30 days and at 3, 6, and 12 months.
How the study is structured. Interventional, single-group (all participants receive the same assigned treatment), open-label Phase 2 study. Participants receive oral ruxolitinib twice daily plus a 4-week reduced-intensity HLH-94 induction (dexamethasone and intravenous etoposide with dosing adjusted by response). After induction, ruxolitinib may continue in 28-day cycles for up to six months if there is no progression or unacceptable toxicity. Study procedures include blood sample collection, abdominal imaging, and bone marrow or lymph node biopsies as needed; participants are followed after treatment at 30 days and at about 3, 6, and 12 months.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on hemophagocytic lymphohistiocytosis
Important dates
- Study start
- Oct 1, 2024
- Primary completion
- Dec 31, 2028 (estimated)
- Study completion
- Nov 30, 2029 (estimated)
- Target enrollment
- 54 participants (estimated)
- Last updated on registry
- Sep 21, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Jerry Lee, MD, MSc, MPhil
- Collaborators
- Incyte Corporation
- UC Hematological Malignancies Consortium (UCHMC)
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- UCSF Hematopoietic Malignancies Clinical Trial Recruitment 📞 877-827-3222 ✉ HDFCCC.Heme@ucsf.edu
- Claudia Ramos ✉ Claudia.Ramos@ucsf.edu
Participating sites (4)
- University of California, IrvineRecruiting
Irvine, California, 92697 · United States
- Vanessa Lopez · vanescl1@hs.uci.edu
- Elizabeth Brem, MD
- University of California Davis Comprehensive Cancer CenterRecruiting
Sacramento, California, 95817 · United States
- Kylie Blaisdell · kyblaisdell@health.ucdavis.edu
- Hildy Donner · hhdonner@health.ucdavis.edu
- Francisco Socola, MD
- University of California, San DiegoRecruiting
San Diego, California, 92093 · United States
- Kimberly Aguilar · k1aguilar@health.ucsd.edu
- Anthony Nguyen, MD
- University of California, San FranciscoRecruiting
San Francisco, California, 94143 · United States
- UCSF Hematopoietic Malignancies Clinical Trial Recruitment · HDFCCC.Heme@ucsf.edu
- · 877-827-3222 · cancertrials@ucsf.edu
- Jerry Lee, MD
- Aaron Logan, MD, PhD
Terms used on this page · explanations by MedicalUpdates.ai
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- investigational agent
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- sponsor
- The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
- CrCl
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- principal investigator
- The doctor or scientist responsible for running the study at a site or overall.
- natural history
- A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
- chimeric antigen receptor
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- PRIMARY OBJECTIVE
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- stratified
- Randomisation done separately within subgroups, such as age bands or disease severity, so that each group contains a similar mix.
- progression-free survival
- The length of time during and after treatment that a person lives without the condition getting worse, as defined by the study.
- overall survival
- The length of time from the start of the study or treatment that participants are alive, whatever the cause of death.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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