Ruxolitinib for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (RISE) (RISE)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS)
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tania Jain, MBBS; Phone Number: 4109557035; Email: tjain2@jhmi.edu
• Study Contact Backup: Name: Mary Amanda Stevens, MD; Email: msteve35@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients of age 18 or older
• Diagnosis of for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) per ASTCT consensus criteria
• Patients must have an elevated ferritin (>2 × ULN) at time of infusion and/or have a ferritin count that is rapidly rising (per clinical assessment) and at least 2 of the following manifestations as described in the 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)
• Hypofibrinogenemia (<150 mg/dL or <LLN)
• Hemophagocytosis in bone marrow or other tissue

• Grade 1 cytopenias (new onset, worsening, or refractory) defined as:

  • Anemia (Hgb) <LLN* - 10.0 g/dL(gr1)
  • Neutropenia (ANC) 1,000 - 1,499/µL (Gr1)
  • Thrombocytopenia <LLN - 75,000/µL (Gr1)
• Lactate dehydrogenase elevations (>ULN)
• Other coagulation abnormalities (e.g. elevated PT/PTT)
• Direct hyperbilirubinemia
• New-onset splenomegaly that is palpable ≥5 cm below costal margin or >450cc on imaging
• Fever of 100.4 or greater (new or persistent)
• Neurologic changes greater than baseline that are consistent with a grade 1 Immune Effector Cell Encephalopathy (ICE) Score or greater

• Pulmonary manifestations

  • Gr 2 Hypoxia with decreased oxygen saturation with exercise (e.g. pulse ox <88%)
  • pulmonary infiltrates
  • pulmonary edema with radiologic findings and moderate dyspnea on exertion

• New onset renal insufficiency defined by:

  • an absolute increase in serum creatinine of ≥0.3 mg/dL within 48 hours.
  • A baseline increase in serum creatinine of ≥1.5 times within the prior 7 days.

  • Oliguria defined as urine volume <0.5 mL/kg/h for at least 6 hours.

    • Hypertriglyceridemia (fasting level, >265 mg/dL‖)
• Patients who have received a CAR T product, commercially available or investigational, will be allowed to enroll
• Eastern Cooperative Oncology Group (ECOG) Performance Score43 of 0-2
• Patients may be treatment naïve for the IECH-HS diagnosis or may have received prior or ongoing treatment. Corticosteroids can be continued along with RUX initiation as noted above.
• Patient is able to take oral medication or is willing to have an NG tube placed if unable to take oral medication. Patients in whom NG tube was placed due to acute decompensation (resulting in an ECOG of >2), will be excluded.
• Willing and able to sign an informed consent form

Exclusion Criteria:

• 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.

Note: If a participant has a positive screening test result for SARS-CoV-2 infection, the participant should be excluded until test normalization and clinical recovery.

• Any prior investigational agent used to treat IEC-HS
• Patient on treatment with rifampin, St Johns wart or other JAK inhibitors
• Patient is unable to tolerate medicine administration either orally or via NG tube.
• Known history of allergic reaction to ruxolitinib
• History of clinically significant or uncontrolled cardiac disease, including recent (within the last 12 months) unstable angina or acute myocardial infarction, or New York Heart Association Class III or IV congestive heart failure, or clinically significant arrhythmias not controlled by medication. Participants with a pacemaker and well-controlled rhythm for at least 1 month before the first dose of study treatment will be allowed.
• Any major surgery within 28 days before the first dose of study treatment.
• Active HBV (or at risk of reactivation), defined as follows: positive HBsAg result (laboratory test required at screening), and/or positive total anti-HBc result (laboratory test required at screening), and/or quantitative HBV DNA test result greater than the lower limits of detection of the assay (if known; laboratory test not required for eligibility purpose, but can be done as part of screening if available locally). Note: Participants with no prior history of HBV infection who have been vaccinated against HBV and who have a positive anti-HBs as the only evidence of prior exposure may participate in the study.
• Active HCV, defined as follows: positive anti-HCV result (laboratory test required at screening) and quantitative HCV RNA test result greater than the lower limits of detection of the assay (laboratory test only required if anti-HCV-positive, can be done as part of screening if available locally).

Note: Anti-HCV-positive participants who received and completed treatment for HCV that was intended to eradicate the virus may participate if HCV RNA levels are undetectable at least 12 weeks after the last dose of therapy. Anti-HCV-positive participants with no available confirmatory negative HCV RNA test results will be excluded.

• Known history of HIV (1/2 antibodies).
• Any condition or circumstance that would, in the investigator's judgment, interfere with full participation in the study (eg, unable, unlikely, or unwilling to comply with the dose schedule and study evaluations, active alcohol or drug addiction), including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ruxolitinib (RUX) therapy; Patients will receive ruxolitinib at a dose of 5 mg twice a day if platelets are under 30,000/µL, ruxolitinib 10 mg twice a day if platelets are ≥30,000/µL but under 50,000/µL, or ruxolitinib 15 mg twice a day if platelets are ≥50,000/µL at the start of treatment. If a favorable response to ruxolitinib is noted (as defined in the protocol), patients will continue on treatment for at least 8 weeks if it is tolerated without significant side effects.

Drug: Ruxolitinib; In 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.; Other Names: JAKAFI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 weeks
Number of Adverse events	Quantify number of Adverse events as monitored by CTCAE v6.0.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 week
Complete response (CR) assessment	Number of patients who achieve a complete response at 8 weeks	8 weeks
Median time to achieve FR	Determine the median time for patients with IEC-HS to achieve at least FR with RUX.	8 weeks
Overall survival	Overall survival at 3-months in patients who receive at least 1 dose of RUX for IEC-HS	3 months
Event-free survival	Event free survival at 3-months in patients who receive at least 1 dose of RUX for IEC-HS. An "Event" includes addition of another therapeutic agent or change in treatment for IEC-HS, death, relapse of IEC-HS, and relapse of primary disease.	3 months
Participants With Improvement of cytopenias	Proportion of patients whose grade 3-4 cytopenias improve to grade 2 or better on treatment with RUX.	8 weeks
Intensive care admission rate	Proportion of patients who are admitted to intensive care (ICU for grade 3 or higher adverse events related to IEC-HS after initiation of RUX.	8 weeks
Participants With Development of infections, worsening cytopenias, and/or new transfusion dependence	Proportion of patients who develop culture/assay-proven infections, worsening cytopenias, and/or new transfusion dependence upon treatment with RUX.	8 weeks
Overall response of disease	Overall response of underlying disease at Day 90 post CAR T treatment in patients who develop IEC-HS.	3 months
Rate of relapse	Rate of relapse of IEC-HS following discontinuation of RUX.	6 months
Time until start of new therapy of IEC-HS	Determine the amount of time between completion of RUX and the start of additional therapy for IEC-HS if such is needed.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal RUX treatment duration	Determine the optimal duration of RUX therapy	6 months
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.	8 weeks
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.	8 weeks

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: Tania Jain, MBBS, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CAR T; ruxolitinib; IEC-HS
• Additional Relevant MeSH Terms: ruxolitinib
• Other Study ID Numbers: J2632; IRB00544306 (Other Identifier: JHM IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No