Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH)
NCT ID: NCT06160791
Last Updated: 2025-12-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
36 participants
INTERVENTIONAL
2024-10-01
2029-11-30
Brief Summary
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Detailed Description
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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
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (ruxolitinib, dexamethasone, etoposide)
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.
Ruxolitinib
Administered Orally (PO)
Etoposide
Administered IV
Dexamethasone
Administered PO or IV
Non-interventional Imaging
Participants undergo abdominal ultrasound and/or magnetic resonance imaging (MRI)
Research Biopsy
Bone marrow biopsy and lymph node biopsy will be obtained during screening and as clinically indicated throughout the trial.
Biospecimen Collection
Undergo blood sample collection
Interventions
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Ruxolitinib
Administered Orally (PO)
Etoposide
Administered IV
Dexamethasone
Administered PO or IV
Non-interventional Imaging
Participants undergo abdominal ultrasound and/or magnetic resonance imaging (MRI)
Research Biopsy
Bone marrow biopsy and lymph node biopsy will be obtained during screening and as clinically indicated throughout the trial.
Biospecimen Collection
Undergo blood sample collection
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
ALL
No
Sponsors
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Incyte Corporation
INDUSTRY
UC Hematological Malignancies Consortium (UCHMC)
UNKNOWN
Jerry Lee, MD, MSc, MPhil
OTHER
Responsible Party
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Jerry Lee, MD, MSc, MPhil
Assistant Clinical Professor
Principal Investigators
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Jerry Lee, MD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
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University of California, Irvine
Irvine, California, United States
University of California, San Francisco
San Francisco, California, United States
Countries
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Central Contacts
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UCSF Hematopoietic Malignancies Clinical Trial Recruitment
Role: CONTACT
Phone: 877-827-3222
Email: [email protected]
Facility Contacts
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Hildy Donner
Role: primary
Vanessa Lopez
Role: backup
UCSF Hematopoietic Malignancies Clinical Trial Recruitment
Role: primary
Role: backup
Other Identifiers
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NCI-2023-09578
Identifier Type: REGISTRY
Identifier Source: secondary_id
232513
Identifier Type: -
Identifier Source: org_study_id