Histiocytic NeoplasmsPhase 2NCT06411821
Ulixertinib in People With Histiocytic Neoplasms
A Phase 2 study testing Ulixertinib in people with Histiocytic Neoplasms, run by Memorial Sloan Kettering Cancer Center at 8 sites in United States.
Trial summary
The researchers are doing this study is to find out whether ulixertinib is an effective and safe treatment for people with histiocytic neoplasms. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Histiocytic Neoplasms
- What is being tested?
- Ulixertinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 8 sitesUnited States
- Study dates
- 7 May 2024to May 2027
- Phase
- Phase 2
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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)
- °≥ 16 years- 1.7 (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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Rona Yaeger, MD contact
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge (Consent Only)
Basking Ridge, New Jersey, 07920
Eli Diamond, MD, 212-610-0243
- Recruiting
Memorial Sloan Kettering Suffolk-Commack (Consent Only)
Commack, New York, 11725
Eli Diamond, MD, 212-610-0243
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Eli Diamond, MD, 212-610-0243
- Recruiting
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Eli Diamond, MD, 212-610-0243
- Recruiting
Memorial Sloan Kettering Bergen (Consent Only)
Montvale, New Jersey, 07645
Eli Diamond, MD, 212-610-0243
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Eli Diamond, MD, 212-639-7576
Rona Yaeger, MD, 646-888-5109
- Recruiting
Mayo Clinic (Data Collection Only)
Rochester, Minnesota, 55905
Jithma Abeykoon, MD, 507-284-2511, abeykoon.jithma@mayo.edu
- Recruiting
Memorial Sloan Kettering Nassau (Consent Only)
Uniondale, New York, 11553
Eli Diamond, MD, 212-610-0243
About this study
Official title: Phase 2 Trial of Ulixertinib for Patients With Histiocytic Neoplasms
The researchers are doing this study is to find out whether ulixertinib is an effective and safe treatment for people with histiocytic neoplasms.
- Conditions
- Histiocytic Neoplasms
- Being tested
- Ulixertinib
- Keywords
- Ulixertinib (BVD-523), 23-282, Mitogen-activated protein kinase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UlixertinibDrug
Also called BVD-523
300 mg twice daily, for every 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort) | Experimental | Patients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle. Receives: Drug: Ulixertinib |
| No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort) | Experimental | Patients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle. Receives: Drug: Ulixertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2024
- Study start7 May 2024
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Histiocytic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter phase 2 trial evaluating the efficacy and safety of monotherapy ulixertinib, an oral selective extracellular signalregulated kinase (ERK) inhibitor, for patients with histiocytic neoplasms:
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Responsible party
- Sponsor
- Investigators
- Eli Diamond, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06411821
- Sponsor's protocol ID
- 23-282
- Status last verified
- Oct 2026
- First submitted
- 8 May 2024
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Ulixertinib for Patients With Histiocytic Neoplasms
- ClinicalTrials.gov ID
- NCT06411821
- Acronym / sponsor ID
- 23-282
- Conditions
- Histiocytic Neoplasms
- Keywords
- Ulixertinib (BVD-523), 23-282, Mitogen-activated protein kinase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- BioMed Valley Discoveries, Inc
- Study start
- 7 May 2024 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 13 May 2024 (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.
The researchers are doing this study is to find out whether ulixertinib is an effective and safe treatment for people with histiocytic neoplasms.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Multicenter phase 2 trial evaluating the efficacy and safety of monotherapy ulixertinib, an oral selective extracellular signalregulated kinase (ERK) inhibitor, for patients with histiocytic neoplasms:
| Arm | Type | Receives |
|---|---|---|
| Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort) | Experimental | Drug: UlixertinibPatients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle. |
| No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort) | Experimental | Drug: UlixertinibPatients in this study will receive ulixertinib, starting at 300 mg twice daily, for every 28-day cycle. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (27 listed)
- 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)
Key exclusion criteria (13 listed)
- 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)
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 |
|---|---|---|
| UlixertinibAlso: BVD-523300 mg twice daily, for every 28-day cycle. | Drug | Mitogen-activated protein kinase (MAPK) pathway mutation (primary cohort), No Mitogen-activated protein kinase (MAPK) pathway mutation identified (exploratory cohort) |
Primary outcome
overall response rate
Time frame: 1 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
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 15 Oct 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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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.
Rona Yaeger, MD contact
Eli Diamond, MD principal investigator
Memorial Sloan Kettering Cancer Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ulixertinib in people with Histiocytic Neoplasms, run by Memorial Sloan Kettering Cancer Center at 8 sites 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 27 inclusion and 13 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 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Eli Diamond, MD (212-610-0243, diamone1@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall response rate (time frame: 1 year). 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 15 Oct 2026.