Recruiting
Phase 1

Ruxolitinib

Sponsor:

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Code:

NCT07424222

Conditions

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

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Ruxolitinib

Study Details

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)

Study ID

NCT07424222

Start date

Jul 15, 2026

Status verified date

Jul, 2026

Completion date

Feb 1, 2029

Anticipated

Primary completion date

Jul 1, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 Design

Enrollment

16 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

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.

Primary outcome measure

  • Number of Participants with Clinical Response [ Time Frame: 8 weeks ]
  • Number of Adverse events [ Time Frame: 8 weeks ]

Central Contacts and Locations

Central contacts

Tania Jain, MBBS

4109557035tjain2@jhmi.edu

Mary Amanda Stevens, MD

msteve35@jhmi.edu

Locations

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Tania Jain, MBBS

410-955-3008jhmeirb@jhmi.edu

Natalie Gahres, RN

ngahres1@jh.edu

More Information

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last update posted

Jul 28, 2026

Last verified

Jul, 2026

Keywords

  • CAR T
  • IEC-HS
  • ruxolitinib

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins on 2026-07-28.