Hemophagocytic LymphohistiocytosesPhase 2NCT06160791
Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH)
A Phase 2 study testing Ruxolitinib, Etoposide and Dexamethasone in people with Hemophagocytic Lymphohistiocytoses, run by Jerry Lee, MD, MSc, MPhil at 4 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemophagocytic Lymphohistiocytoses
- What is being tested?
- Ruxolitinib, Etoposide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Oct 2024to 30 Nov 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Claudia Ramos contact
United States4 sites, 4 recruiting
- Recruiting
University of California, Irvine
Irvine, California, 92697
Vanessa Lopez, vanescl1@hs.uci.edu
Elizabeth Brem, MD
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Kylie Blaisdell, kyblaisdell@health.ucdavis.edu
Hildy Donner, hhdonner@health.ucdavis.edu
- Recruiting
University of California, San Diego
San Diego, California, 92093
Kimberly Aguilar, k1aguilar@health.ucsd.edu
Anthony Nguyen, MD
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
UCSF Hematopoietic Malignancies Clinical Trial Recruitment, HDFCCC.Heme@ucsf.edu
877-827-3222, cancertrials@ucsf.edu
About this study
Official title: Frontline Ruxolitinib With De-Intensified HLH-94 for Adult Hemophagocytic Lymphohistiocytosis (HLH): A Multicenter, Single-Arm Phase 2 Study
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Being tested
- Ruxolitinib, Etoposide, Dexamethasone, Non-interventional Imaging, Research Biopsy
- Keywords
- HLH-94
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called INCB18424, Oral JAK
Administered Orally (PO)
EtoposideDrug
Also called Toposar, Lastet
Administered IV
DexamethasoneDrug
Also called Dexa
Administered PO or IV
Non-interventional ImagingProcedure or surgery
Also called Ultrasound, Magnetic resonance imaging (MRI)
Participants undergo abdominal ultrasound and/or magnetic resonance imaging (MRI)
Research BiopsyProcedure or surgery
Also called Biopsy
Bone marrow biopsy and lymph node biopsy will be obtained during screening and as clinically indicated throughout the trial.
Biospecimen CollectionProcedure or surgery
Also called Specimen collection
Undergo blood sample collection
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ruxolitinib, dexamethasone, etoposide) | Experimental | During induction therapy, participants receive ruxolitinib orally (PO) twice daily (BID) plus de-intensified HLH-94 induction with dexamethasone PO or intravenously (IV) once daily (QD) or BID for 4 weeks and etoposide IV twice a week (BIW) for 2 weeks and then based on response, once a week (QW) for another 2 weeks in the absence of disease progression or unacceptable toxicity. After induction therapy, participants receive continuation therapy with ruxolitinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for a total of up to 6 months after first administration of study drug in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ruxolitinib; Drug: Etoposide; Drug: Dexamethasone; Procedure: Non-interventional Imaging; Procedure: Research Biopsy; Procedure: Biospecimen Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR)
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.
Measured: 4 weeks
Secondary outcomes (9)
Proportion of participants reporting high-grade adverse events
Safety analyses will be descriptive and performed based on the safety population, defined as patients who received at least one dose of study drug. Serious adverse events (SAEs), adverse events (AEs) ≥ grade 3, and AEs resulting in discontinuation of treatment, withdrawal from the study, and deaths on-study will be tabulated.
Measured: Up to 1 year
Best Response Rate
The proportion of responders by best response defined as a complete response (CR), complete response with incomplete hematologic recovery, partial response (PR) or stable disease (SD)) using a physician developed response criteria will be reported.
Measured: Up to 1 year
Median Time to Best Response
The median time in months from the time of treatment initiation until participants best response at 12 months after the end of continuation therapy will be reported.
Measured: Up to 12 months after the end of continuation therapy, approximately 2 years total
Median Duration of Best Response
The median time in months from the participants obtained a best response from until 12 months after the end of continuation therapy, participant withdrawal, or death will be reported.
Measured: Up to 12 months after the end of continuation therapy, approximately 2 years total
Median progression free survival (PFS)
PFS is defined as the median number of months from first dose to disease relapse, progression, or death, whichever occurs first using using Kaplan-Meier methods.
Measured: Up to 1 year
Median overall survival (OS)
OS is defined as the median number of months from first dose to until death or study discontinuation, whichever occurs first using using Kaplan-Meier methods.
Measured: Up to 1 year
Median time from the diagnosis of hemophagocytic lymphohistiocytosis (HLH) to diagnosis of cancer
The duration of time in days from the diagnosis of hemophagocytic lymphohistiocytosis (HLH) to the diagnosis of cancer will be reported.
Measured: Up to 1 year
Median time from diagnosis of malignancy-associated HLH to initiation of cancer-directed therapy
The duration of time in days from the diagnosis of malignancy-associated hemophagocytic lymphohistiocytosis to the initiation of cancer-directed therapy will be reported using Kaplan-Meier methods.
Measured: Up to 1 year
Number of different adjunctive therapies
The number of adjunctive therapies for HLH will be reported by type, frequency, and indication.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start1 Oct 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion30 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophagocytic LymphohistiocytosesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jerry Lee, MD, MSc, MPhil
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation, UC Hematological Malignancies Consortium (UCHMC)
- Responsible party
- Sponsor-investigator, Jerry Lee, MD, MSc, MPhil, University of California, San Francisco
- Investigators
- Jerry Lee, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06160791
- Sponsor's protocol ID
- 232513
- Other IDs
- NCI-2023-09578
- Status last verified
- Sep 2026
- First submitted
- 29 Nov 2023
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be shared with study collaborators during the course of the study.
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frontline Ruxolitinib With De-Intensified HLH-94 for Adult Hemophagocytic Lymphohistiocytosis (HLH): A Multicenter, Single-Arm Phase 2 Study
- ClinicalTrials.gov ID
- NCT06160791
- Acronym / sponsor ID
- 232513
- Conditions
- Hemophagocytic Lymphohistiocytoses
- Keywords
- HLH-94
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Jerry Lee, MD, MSc, MPhilUniversity, hospital or other
- Collaborators
- Incyte Corporation, UC Hematological Malignancies Consortium (UCHMC)
- Study start
- 1 Oct 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 30 Nov 2029 (estimated)
- First posted
- 7 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ruxolitinib, dexamethasone, etoposide) | Experimental | Drug: Ruxolitinib, Drug: Etoposide, Drug: Dexamethasone, Procedure: Non-interventional Imaging, Procedure: Research Biopsy, Procedure: Biospecimen CollectionDuring induction therapy, participants receive ruxolitinib orally (PO) twice daily (BID) plus de-intensified HLH-94 induction with dexamethasone PO or intravenously (IV) once daily (QD) or BID for 4 weeks and etoposide IV twice a week (BIW) for 2 weeks and then based on response, once a week (QW) for another 2 weeks in the absence of disease progression or unacceptable toxicity. After induction therapy, participants receive continuation therapy with ruxolitinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for a total of up to 6 months after first administration of study drug in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibAlso: INCB18424, Oral JAKAdministered Orally (PO) | Drug | Treatment (ruxolitinib, dexamethasone, etoposide) |
| EtoposideAlso: Toposar, LastetAdministered IV | Drug | Treatment (ruxolitinib, dexamethasone, etoposide) |
| DexamethasoneAlso: DexaAdministered PO or IV | Drug | Treatment (ruxolitinib, dexamethasone, etoposide) |
| Non-interventional ImagingAlso: Ultrasound, Magnetic resonance imaging (MRI)Participants undergo abdominal ultrasound and/or magnetic resonance imaging (MRI) | Procedure or surgery | Treatment (ruxolitinib, dexamethasone, etoposide) |
| Research BiopsyAlso: BiopsyBone marrow biopsy and lymph node biopsy will be obtained during screening and as clinically indicated throughout the trial. | Procedure or surgery | Treatment (ruxolitinib, dexamethasone, etoposide) |
| Biospecimen CollectionAlso: Specimen collectionUndergo blood sample collection | Procedure or surgery | Treatment (ruxolitinib, dexamethasone, etoposide) |
Primary outcome
Overall response rate (ORR)
Time frame: 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.
9 secondary outcomes
Proportion of participants reporting high-grade adverse events
Time frame: Up to 1 year
Best Response Rate
Time frame: Up to 1 year
Median Time to Best Response
Time frame: Up to 12 months after the end of continuation therapy, approximately 2 years total
Median Duration of Best Response
Time frame: Up to 12 months after the end of continuation therapy, approximately 2 years total
Median progression free survival (PFS)
Time frame: Up to 1 year
Median overall survival (OS)
Time frame: Up to 1 year
Median time from the diagnosis of hemophagocytic lymphohistiocytosis (HLH) to diagnosis of cancer
Time frame: Up to 1 year
Median time from diagnosis of malignancy-associated HLH to initiation of cancer-directed therapy
Time frame: Up to 1 year
Number of different adjunctive therapies
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Individual participant dataSharing planned: Yes. De-identified data will be shared with study collaborators during the course of the study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Claudia Ramos contact
Jerry Lee, MD principal investigator
University of California, San Francisco
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib, Etoposide and Dexamethasone in people with Hemophagocytic Lymphohistiocytoses, run by Jerry Lee, MD, MSc, MPhil at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact UCSF Hematopoietic Malignancies Clinical Trial Recruitment (877-827-3222, HDFCCC.Heme@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.