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Ulixertinib for Histiocytic Neoplasms

This study is testing a drug called ulixertinib to see if it is a safe and effective treatment for people with histiocytic neoplasms (a group of rare disorders where too many immune cells called histiocytes build up in organs and tissues). Researchers want to see if ulixertinib can help shrink or control these neoplasms. You might be able to join if you are 12 years or older and have a confirmed histiocytic neoplasm. The study aims to enroll 38 participants. The main goal is to measure how many people respond to the treatment after one year. The current status of this study is unclear.

Study design
This is an interventional study, meaning participants will receive a specific treatment. It plans to enroll 38 participants.
What's involved
Participants will take ulixertinib (300 mg) twice daily for every 28-day cycle. Not specified in the trial record.
Compensation
Not stated in the trial record.
Follow-up
The study measures overall response rate at 1 year, suggesting follow-up for at least that duration.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT06411821

Ulixertinib in People With Histiocytic Neoplasms

Recruiting
PHASE2Ages 12+InterventionalTreatment
Memorial Sloan Kettering Cancer Center
~38 participants
Updated 2026-05-28 on ClinicalTrials.gov
What's tested:Ulixertinib

At a glance

Recruiting sites
8 of 8 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
overall response rate
Measured over 1 year

Conditions

Histiocytic Neoplasms

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NCT06411821

Where you'd take part

This study runs at 8 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • Mayo Clinic (Data Collection Only)

    Rochester, Minnesotastudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Basking Ridge (Consent Only)

    Basking Ridge, New Jerseystudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Bergen (Consent Only)

    Montvale, New Jerseystudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New Yorkstudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jerseystudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Nassau (Consent Only)

    Uniondale, New Yorkstudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Suffolk-Commack (Consent Only)

    Commack, New Yorkstudy coordinator listed

    Recruiting

  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)

    Harrison, New Yorkstudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Eli Diamond, MD · PRINCIPAL_INVESTIGATOR · Memorial Sloan Kettering Cancer Center

Who to contact

Eli Diamond, MD
[email protected]
212-610-0243
Email the study team

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Eligibility criteria

Inclusion

Histologically confirmed histiocytic neoplasm or histologic findings consistent with histiocytic neoplasm with confirmatory radiologic or molecular findings. Pathologic examination can be performed at any of the enrolling institutions. This qualification is made because it is well known that biopsies of histiocytic neoplasms are variable and do not always demonstrate "typical" morphologic appearance with all of the classically described elements. As a result, histiocytic neoplasms are not exclusively pathologic diagnoses-rather, they are interpretations of histologic findings in a clinical and radiologic context. These criteria were applied in NCT02649972 and will be applied in this trial
Identified mutation in MAPK pathway genes, including but not limited to ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1, MAP2K2, and NF1 (for primary cohort; no mutation needed for exploratory cohort). Tumor mutation may be identified by tumor sequencing or cfDNA-based sequencing. Concordance between cfDNA and tumor sequencing for BRAFV600E and non-BRAF mutations in histiocytic neoplasms has been documented by our group and others
Measurable disease according to PRC, confirmed by an investigator radiologist
Age (a) ≥18 years prior to interim safety and efficacy analyses or (b) ≥12 years following the interim safety and efficacy analyses
The histiocytic neoplasm must be (a) disease that is recurrent/refractory/persistent despite local therapies, chemotherapy, immunosuppression, or BRAF/MEK inhibitors OR (b) multisystem disease OR (c) single-system disease that is causing end-organ dysfunction and is unlikely to benefit from local or conventional (chemotherapy or immunosuppressive) therapies on the basis of evidence-based guidelines (e.g. symptomatic neurologic-only LCH)
Prior treatment (chemotherapy, immunosuppression, BRAF inhibitor, or MEK inhibitor) is required and the patient must have (a) progressive disease or persistent disease (i.e. having disease measurable by PRC) or (b) intolerance or contraindication to or refusal of, chemotherapy, immunosuppression, BRAF inhibition, or MEK inhibition.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (age ≥ 16) or Lansky 50-100 (age 12-15)
Adequate renal function (according to the Cockcroft-Gault equation; creatinine ≤1.5 times upper limit of normal \[ULN\] or a glomerular filtration rate of ≥50 mL/min)
Pediatric patients (\<18 years old) must have a creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m\^2 or serum creatinine based on age/gender as follows:
\< 13 years- 1.2 (Male),1.2 (Female)
13 to \< 16 years- 1.5 (Male), 1.4 (Female)
The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
Patients with renal impairment deemed the direct result of disease and therefore amenable to improvement with Ulixertinib treatment may be enrolled at the discretion of the treating investigator
Adequate hepatic function (total bilirubin ≤1.5 times ULN, aspartate transaminase \[AST\] and- alanine transaminase \[ALT\] ≤3 times ULN or ≤5 times ULN if attributable to liver involvement by tumor). Patients with hepatic impairment deemed the direct result of disease and therefore amenable to improvement with Ulixertinib treatment may be enrolled at the discretion of the treating investigator. Patients with Gilbert's Syndrome may have total bilirubin ≤3 x ULN.
Adequate bone marrow function (hemoglobin ≥9.0 g/dL, platelets ≥100 x 10\^9 cells/L, absolute neutrophil count ≥1.5 x 10\^9 cells/L). Patients with cytopenias deemed the direct result of disease and therefore amenable to improvement with Ulixertinib treatment may be enrolled at the discretion of the treating investigator.
Adequate cardiac function
Left ventricular ejection fraction \>50% as assessed by multi-gated acquisition or ultrasound or echocardiography and
Corrected QT interval (QTc) \<480 ms according to the Fridericia method (QTcF)
Contraception
For women: a negative pregnancy test for those of child-bearing potential, must be surgically sterile, postmenopausal (no menstrual cycle for at least 12 consecutive months), or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period
For men: must be surgically sterile or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period
For patients aged \<18 years who are not sexually active: abstinence is an acceptable form of contraception. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
Willing and able to participate in the trial and comply with all trial requirements
Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational agent may be included at the discretion of the site PI

Exclusion

Uncontrolled or severe intercurrent medical condition
Receipt of any histiocytic neoplasm-directed therapy (chemotherapy, targeted therapy, biologic) within 28 days or 5 half-lives (whichever is shorter) before the first dose of ulixertinib. Patients previously treated with radiotherapy must have recovered from acute toxicities associated with such treatment
Histiocytic neoplasm mandated for observation-only or first-line local therapy per established guidelines. Examples would include asymptomatic nodal RDD, asymptomatic osseous ECD, or limited cutaneous LCH
Major surgery within 4 weeks of the first dose of ulixertinib
Pregnant, lactating, or breast-feeding (for women)
Any evidence of serious active infections. Patients are allowed to enroll if they have been fever free for at least 48 h
History or current evidence of risk of retinal vein occlusion or central serous retinopathy. Examples of risk factors to be considered would include uncontrolled ocular hypertension or history of hyperviscosity.
Concurrent therapy with drugs known to be strong inhibitors or inducers of CYP1A2, CYP2D6, and CYP3A4
Concurrent therapy with p-glycoprotein inhibitors and sensitive substrates of CYP1A2, CYP2B6, CYP2C8, and CYP3A4/5 with narrow therapeutic indices
Inability to swallow oral medications
Prior stomach or duodenal resection that, in the opinion of the site PI, would affect the breakdown and absorption of the study medications. Patients with a feeding tube will also be excluded, as ulixertinib tablets cannot be taken broken, cracked or otherwise not intact. Note: ulixertinib is primarily absorbed in the duodenum, and therefore the potential inclusion of a patient with any prior stomach or duodenal resection should be discussed with the MSK PI
Concurrent therapy with any investigational agent
Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter). In addition, any drug toxicities should have recovered to grade 1 or less before start of the trial medication

What this trial measures

  • overall response rate1 year

    Best overall response by PET is defined as the best response, according to PRC, recorded from the first day of study treatment until disease progression, recurrence, or death. Complete response Normalization of all lesions' (target and nontarget) SUV to background SUVliver (or SUVbrain for brain lesions) Partial response ≥50% decrease from baseline in sum of SUVs of all target lesions relative to SUVliver (or SUVbrain for brain lesions only) Progressive disease ≥50% increase from nadir in sum of SUV of all target lesions relative to SUVliver (or SUVbrain for brain lesions only), with a minimal absolute increase of 3 units of SUV per target lesion (e.g., SUV 3 to SUV 6) New evaluable lesions deemed to represent unequivocal disease progression\* Stable disease Does not meet other criteria