Ruxolitinib Phosphate in Treating Patients with Secondary Hemophagocytic Syndrome

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.

Trial Phase Phase II

Trial Type Treatment

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