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

NCT07424222 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J2632IRB00544306
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS)

Keywords

CAR T; IEC-HS; ruxolitinib

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Favorable response (FR) assessment

  1 week

• Complete response (CR) assessment

  8 weeks

• Median time to achieve FR

  8 weeks

• Overall survival

  3 months

• Event-free survival

  3 months

Other Outcomes (3)

• Change in immunological biomarker response

  8 weeks

• CAR T cell expansion dynamics following RUX

  8 weeks

• Optimal RUX treatment duration

  6 months

Study Arms (1)

Ruxolitinib (RUX) therapy

EXPERIMENTAL

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

Interventions

Ruxolitinib DRUG

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.

Also known as: JAKAFI

Ruxolitinib (RUX) therapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Incyte Corporation: collaborator

MeSH Terms

Interventions

ruxolitinib

Study Officials

• Tania Jain, MBBS

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tania Jain, MBBS

CONTACT

4109557035; tjain2@jhmi.edu

Mary Amanda Stevens, MD

CONTACT

msteve35@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: February 20, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-05