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Ulixertinib in People With Histiocytic Neoplasms | Clinical Trials | Clareo Health

RECRUITINGPHASE2

Ulixertinib in People With Histiocytic Neoplasms

Phase 2 Trial of Ulixertinib for Patients With Histiocytic Neoplasms

NCT06411821•Memorial Sloan Kettering Cancer Center

Summary

The researchers are doing this study is to find out whether ulixertinib is an effective and safe treatment for people with histiocytic neoplasms.

Eligibility

Age

12 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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 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)
+17 more criteria

Exclusion Criteria

•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
+3 more criteria

Locations (8)

Mayo Clinic (Data Collection Only)

Rochester, Minnesota, United States

Memorial Sloan Kettering Basking Ridge (Consent Only)

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (Consent Only)

Montvale, New Jersey, United States

Memorial Sloan Kettering Suffolk-Commack (Consent Only)

Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, United States

Memorial Sloan Kettering Nassau (Consent Only)

Uniondale, New York, United States

Key Dates

Start Date

May 7, 2024

Primary Completion Date

May 1, 2027

Completion Date

May 1, 2027

Last Updated

December 15, 2025

Enrollment

ESTIMATED participants

Conditions

Histiocytic Neoplasms

Interventions

Ulixertinib

DRUG

Contacts

Eli Diamond, MD

CONTACT

212-610-0243 diamone1@mskcc.org

Rona Yaeger, MD

CONTACT

646-888-5109