Ruxolitinib Phosphate in Treating Patients with Secondary Hemophagocytic Syndrome

This phase II trial studies how well ruxolitinib phosphate works in treating patients with hemophagocytic syndrome. Ruxolitinib phosphate may decrease secondary hemophagocytic syndrome by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

• Patients, or their legally authorized representative, must voluntarily provide written Institutional Review Board (IRB)-approved informed consent
• Patients must meet the diagnostic criteria for HPS (at least 5 of the following): * Fever * Splenomegaly * Cytopenia involving >= 2 cell lines (hemoglobin < 9 g/dL; platelets < 100,000/uL; absolute neutrophil count < 1000/uL) * Hypertriglyceridemia or hypofibrinogenemia * Tissue demonstration of hemophagocytosis * Low or absent natural killer (NK) cell activity * Serum ferritin >= 3000 ug/L * Soluble interleukin (IL)-2 receptor (cluster of differentiation [CD25]) > 2400 U/mL
• In the investigator’s opinion, the patient has the ability to participate fully in the study and comply with all its requirements

Exclusion Criteria

• Central nervous system (CNS) involvement
• Malabsorption
• Known secondary HPS that is otherwise treatable (e.g. non-Hodgkin’s lymphoma)
• Pregnant or lactating female: all females of child-bearing potential must have a negative serum pregnancy test within 7 days of treatment; lactating females must discontinue breast feeding
• Has received any prior systemic therapy, excluding corticosteroids, within 7 days (or 5 half-lives) of treatment
• Estimated creatinine clearance < 15 mL/min
• No active malignancy at the time of enrollment, except nonmelanoma skin cancers or carcinoma in situ; patients with a prior history of malignancy are eligible if their malignancy has been definitely treated or is in remission and does not require ongoing adjuvant or cancer-directed therapies
• Active hepatitis B or hepatitis C or known human immunodeficiency virus (HIV) infection
• Known (and biopsy-confirmed) liver cirrhosis; or, a reported history of liver cirrhosis with a model for end-stage liver disease (MELD) score > 20

PRIMARY OBJECTIVES:

I. To assess the efficacy of ruxolitinib (ruxolitinib phosphate) 15 mg orally (PO) twice daily in patients with hemophagocytic syndrome (HPS).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of ruxolitinib in patients with HPS.

II. To determine the response rate, duration of response, progression-free survival, and overall survival in ruxolitinib treated subjects.

III. To assess inflammatory cytokines and markers of T-cell/macrophage activation (i.e. cytokines, soluble interleukin-2 receptor [sIL-2R], soluble cluster of differentiation 163 [sCD163]) as predictive biomarkers.

OUTLINE:

Patients receive ruxolitinib phosphate PO twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6-12 months thereafter.

Lead Organization
University of Michigan Comprehensive Cancer Center

Principal Investigator
Ryan Wilcox

Primary ID UMCC 2014.112
Secondary IDs NCI-2015-01750, HUM00092921
Clinicaltrials.gov ID NCT02400463