Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS)Phase 1RISENCT07424222
Ruxolitinib for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (RISE)
A Phase 1 study testing Ruxolitinib in people with Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS)
- What is being tested?
- Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2026to 1 Feb 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 31Show fewer
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mary Amanda Stevens, MD contact
United States1 site, 1 recruiting
- Recruiting
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
Tania Jain, MBBS, 410-955-3008, jhmeirb@jhmi.edu
Natalie Gahres, RN, ngahres1@jh.edu
About this study
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.
- Being tested
- Ruxolitinib
- Keywords
- CAR T, IEC-HS, ruxolitinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called JAKAFI
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks
Number of Adverse events
Quantify number of Adverse events as monitored by CTCAE v6.0.
Measured: 8 weeks
Secondary outcomes (11)
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.
Measured: 1 week
Complete response (CR) assessment
Number of patients who achieve a complete response at 8 weeks
Measured: 8 weeks
Median time to achieve FR
Determine the median time for patients with IEC-HS to achieve at least FR with RUX.
Measured: 8 weeks
Overall survival
Overall survival at 3-months in patients who receive at least 1 dose of RUX for IEC-HS
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 8 weeks
Overall response of disease
Overall response of underlying disease at Day 90 post CAR T treatment in patients who develop IEC-HS.
Measured: 3 months
Rate of relapse
Rate of relapse of IEC-HS following discontinuation of RUX.
Measured: 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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study start15 Jul 2026
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS)Studies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Tania Jain, MBBS, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07424222
- Sponsor's protocol ID
- J2632
- Other IDs
- IRB00544306
- Acronym
- RISE
- Status last verified
- Jul 2026
- First submitted
- 13 Feb 2026
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ruxolitinib for Immune Effector Cell Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (RISE)
- ClinicalTrials.gov ID
- NCT07424222
- Acronym / sponsor ID
- RISE / J2632
- Keywords
- CAR T, IEC-HS, ruxolitinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Incyte Corporation
- Study start
- 15 Jul 2026 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Feb 2029 (estimated)
- First posted
- 20 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib (RUX) therapy | Experimental | Drug: RuxolitinibPatients 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- 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)
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibAlso: JAKAFIIn 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. | Drug | Ruxolitinib (RUX) therapy |
Primary outcome
Number of Participants with Clinical Response
Time frame: 8 weeks
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
Time frame: 8 weeks
Quantify number of Adverse events as monitored by CTCAE v6.0.
11 secondary outcomes
Favorable response (FR) assessment
Time frame: 1 week
Complete response (CR) assessment
Time frame: 8 weeks
Median time to achieve FR
Time frame: 8 weeks
Overall survival
Time frame: 3 months
Event-free survival
Time frame: 3 months
Participants With Improvement of cytopenias
Time frame: 8 weeks
Intensive care admission rate
Time frame: 8 weeks
Participants With Development of infections, worsening cytopenias, and/or new transfusion dependence
Time frame: 8 weeks
Overall response of disease
Time frame: 3 months
Rate of relapse
Time frame: 6 months
Time until start of new therapy of IEC-HS
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mary Amanda Stevens, MD contact
Tania Jain, MBBS principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ruxolitinib in people with Immune Effector Associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS), run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tania Jain, MBBS (4109557035, tjain2@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Clinical Response (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.