ClinicalTrials.gov record NCT07424222
Ruxolitinib for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (RISE)
Ruxolitinib for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (RISE)
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This phase 1 pilot study tests oral ruxolitinib in adults with Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis‑like Syndrome (IEC‑HS) occurring after CAR‑T therapy. Ruxolitinib is given twice daily with the starting dose set by the participant's baseline platelet count; treatment is planned for up to 8 weeks with possible taper and continued therapy for some patients up to an additional 6 months. The study will collect safety and response data and perform correlative studies of immunological biomarkers and CAR‑T expansion.
What it is studying. The study is testing ruxolitinib as a treatment for IEC‑HS after CAR‑T therapy, collecting data on safety and clinical response. It also aims to estimate optimal treatment duration, identify immune biomarkers associated with response, and evaluate how CAR‑T cell expansion behaves after ruxolitinib.
What the researchers hope to learn. Gather safety and efficacy information on ruxolitinib for IEC‑HS; estimate optimal duration of ruxolitinib therapy; identify immunological biomarkers associated with response; evaluate dynamics of CAR‑T cell expansion following ruxolitinib treatment.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Ruxolitinib
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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 description and what participation involves
The registry record has no detailed description beyond the summary above.
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants will take oral ruxolitinib twice daily with the starting dose set by platelet count (5, 10, or 15 mg BID). Treatment is planned for up to 8 weeks if tolerated; responders may continue and the dose may be tapered with continued therapy permitted for up to an additional 6 months. The study includes regular clinic visits for safety monitoring and assessments, and correlative testing to study immunological biomarkers and CAR‑T expansion dynamics. Therapy will be stopped for significant toxicity or if the treating physician judges it no longer provides clinical benefit; an NG tube may be used if the participant cannot take oral medication.
How the study is structured. Phase 1, interventional, single-group, open-label study. All participants receive oral ruxolitinib twice daily with dose determined by baseline platelet count. There is no randomization or placebo; participants are assessed for clinical response and adverse events over an initial 8-week period with additional follow-up for some outcomes up to several months.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on hemophagocytic lymphohistiocytosis
Important dates
- Study start
- Jul 15, 2026
- Primary completion
- Jul 1, 2028 (estimated)
- Study completion
- Feb 1, 2029 (estimated)
- Target enrollment
- 16 participants (estimated)
- Last updated on registry
- Jul 28, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Collaborators
- Incyte Corporation
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Tania Jain, MBBS 📞 4109557035 ✉ tjain2@jhmi.edu
- Mary Amanda Stevens, MD ✉ msteve35@jhmi.edu
Participating sites (1)
- The Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsRecruiting
Baltimore, Maryland, 21287 · United States
- Tania Jain, MBBS · 410-955-3008 · jhmeirb@jhmi.edu
- Natalie Gahres, RN · ngahres1@jh.edu
Terms used on this page · explanations by MedicalUpdates.ai
- CAR-T
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- biomarkers
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- × ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- CRS
- A reaction in which the immune system releases a large amount of signalling proteins at once, causing fever and sometimes low blood pressure or breathing problems. It can occur after some immune therapies, such as CAR-T cells or bispecific antibodies.
- refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- ANC
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- investigational
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- informed consent form
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- Life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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