Frontline Ruxolitinib With De-Intensified HLH-94 for Adult Hemophagocytic Lymphohistiocytosis (HLH): A Multicenter, Single-Arm Phase 2 Study
Jerry Lee, MD, MSc, MPhil
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.
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 t…
Interventions
- DrugRuxolitinib
Administered Orally (PO)
- DrugEtoposide
Administered IV
- DrugDexamethasone
Administered PO or IV
- ProcedureNon-interventional Imaging
Participants undergo abdominal ultrasound and/or magnetic resonance imaging (MRI)
- ProcedureResearch Biopsy
Bone marrow biopsy and lymph node biopsy will be obtained during screening and as clinically indicated throughout the trial.
- ProcedureBiospecimen Collection
Undergo blood sample collection
Locations (3)
- University of California, IrvineIrvine, California
- University of California Davis Comprehensive Cancer CenterSacramento, California
- University of California, San FranciscoSan Francisco, California