Ruxolitinib With De-Intensified HLH-94 for the Treatment of Hemophagocytic Lymphohistiocytosis (HLH)

Exclusion Criteria

• •Participant is receiving or received any other investigational agent within 1 week of the first dose of treatment.
• •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