This is a pilot study to gather information about safety and efficacy of using ruxolitinib (RUX) to treat Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) occurring after CAR-T therapy. In addition, correlative studies will be done to 1) estimate the optimal duration of RUX therapy, 2) to identify immunological biomarkers associated with response (3) To evaluate the dynamics of CAR T expansion following RUX treatment.
Oral RUX will be administered twice daily, with dosing determined by the participant's baseline platelet count. Treatment will continue for up to 8 weeks unless significant adverse events occur or the treating physician concludes that the therapy is no longer providing clinical benefit.
The study expects to accrue 16 evaluable patients diagnosed with IEC-HS over 2 years.
Patients of age 18 or older
Diagnosis of for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) per ASTCT consensus criteria
Onset with resolving/resolved CRS or worsening inflammatory response after initial improvement with CRS-directed therapy
Hepatic transaminase elevation§ (>5 × ULN (if baseline was normal) or >5 × baseline if baseline was abnormal)
Life expectancy greater than 6 months
Patients with known active malignancy or known progressive underlying disease
Women who are pregnant or breastfeeding. Women must also refrain from breastfeeding during the course of study and for 60 days after the last dose of study treatment.
Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. Participants with acute infection requiring antibiotic, antifungal, or antiviral treatment use should delay screening/enrollment until the course of antibiotic antifungal, or antiviral therapy has been completed and the infection is not active anymore.
Single group
Ruxolitinib
DrugIn this study, Ruxolitinib will be supplied as 5 mg tablets which will be administered orally twice daily (BID) as an open-label, investigational product. Ruxolitinib dosing based on platelet numbers: * 5 mg twice a day if platelets are under 30,000/µL, * 10 mg twice a day if platelets are more than or equal to 30,000/µL but less than 50,000/µL, or * 15 mg twice a day if platelets are more than or equal to 50,000/µL Patients who respond may continue treatment for at least 8 weeks. Therapy will be discontinued for significant toxicity or evidence of IEC-HS progression. After 8 weeks, the dose may be tapered as clinically appropriate, with continued therapy permitted for up to 6 additional months if clinical benefit persists.
Number of Participants with Clinical Response
Determine clinical response at 8 weeks of RUX therapy. Clinical response (CLR) is defined as complete response, partial response or favorable response per below criteria in section 6.2 of the protocol.
Number of Adverse events
Quantify number of Adverse events as monitored by CTCAE v6.0.
Favorable response (FR) assessment
Proportion of patients who are treated with ruxolitinib (RUX) for IEC-HS and who achieve at least a favorable response (FR) at week 1.
Complete response (CR) assessment
Number of patients who achieve a complete response at 8 weeks
Median time to achieve FR
Determine the median time for patients with IEC-HS to achieve at least FR with RUX.
Overall survival
Overall survival at 3-months in patients who receive at least 1 dose of RUX for IEC-HS
Change in immunological biomarker response
Evaluate changes in immunological biomarkers of inflammation (such as ferritin, fibrinogen, and triglycerides) and cytokine profiles known to be associated with IEC-HS.
CAR T cell expansion dynamics following RUX
Evaluate dynamics of CAR T expansion following RUX treatment by monitoring CAR T-cell expansion and persistence patterns with RUX treatment by using fluorescence-activated cell sorting (FACS) to track CAR T-cell kinetics throughout treatment.
Optimal RUX treatment duration
Determine the optimal duration of RUX therapy
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
Incyte Corporation
Collaborator
