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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Jerry Lee, MD, MSc, MPhil · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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: 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

• Hemophagocytic Lymphohistiocytoses

Interventions

Type	Name	Description
DRUG	Ruxolitinib	Administered Orally (PO)
DRUG	Etoposide	Administered IV
DRUG	Dexamethasone	Administered PO or IV
PROCEDURE	Non-interventional Imaging	Participants undergo abdominal ultrasound and/or magnetic resonance imaging (MRI)
PROCEDURE	Research Biopsy	Bone marrow biopsy and lymph node biopsy will be obtained during screening and as clinically indicated throughout the trial.
PROCEDURE	Biospecimen Collection	Undergo blood sample collection

Timeline

• Start date: 2024-10-01
• Primary completion: 2027-12-31
• Completion: 2029-11-30
• First posted: 2023-12-07
• Last updated: 2026-04-13

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study