SJ901: Mirdametinib for Low-Grade Glioma in Children and Young Adults
This study is testing a drug called mirdametinib for children, adolescents, and young adults (ages 2 to 24) who have low-grade glioma (a type of brain tumor) that has come back or is getting worse. Mirdametinib works by targeting a specific pathway in the body called MEK. The study aims to find the safest and most effective dose of mirdametinib, and to see how well it works to shrink tumors. To join, you need to have a confirmed or suspected low-grade glioma and enough tumor tissue for review. The study is currently looking for 132 participants, but its overall status is unclear.
- Study design
- This is an open-label study, meaning everyone knows what treatment is being given. It is a Phase 1/2 study, planning to enroll 132 participants.
- What's involved
- Mirdametinib is taken by mouth, NG tube, or G-tube twice a day for 28 days in each course. The study will involve monitoring safety and how the drug is processed by the body.
- Compensation
- Not stated in the trial record.
- Follow-up
- Safety will be monitored for up to 25 months after starting mirdametinib treatment. Drug levels will be measured on days 1 and 15 of the first course.
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NCT04923126
SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma
Recruiting
PHASE1Ages 2–24InterventionalTreatmentSt. Jude Children's Research HospitalInvestigator-initiated
~132 participants
Updated 2026-02-04 on ClinicalTrials.gov
What's tested:Mirdametinib
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 1: Estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma.
Measured over 1 month after start of mirdametinib treatment
+7 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesTennessee1
Study leadership
- Giles W. Robinson, MD · PRINCIPAL_INVESTIGATOR · St. Jude Children's Research Hospital
- Anna Vinitsky, MD, MS · PRINCIPAL_INVESTIGATOR · St. Jude Children's Research Hospital
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Participants with histologically confirmed or suspected low-grade glioma, including neuronal and mixed neuronal-glial tumors
Participant must have adequate tumor tissue from primary and/or relapsed tumor for central pathology review
For Phase 1: Projected to be ≥ 2 years and \< 25 years at the time of study enrollment
Participant's body surface area (BSA) at time of study enrollment must fall within the range outlined in the protocol for the specific dose level under evaluation:
Phase 1: Dose Finding/Dose-escalation
For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation.
Phase 2: All Cohorts:
For Phase 2 of the study the upper BSA restrictions will be removed.
Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines
Participant must be ≥ 2 years and \< 25 years of age at the time of enrollment
Participant's BSA at time of study enrollment must fall within the range outlined below for the specific dose level under evaluation:
Phase 1: Dose-finding/Dose-escalation
For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation.
Phase 2: All Cohorts
For Phase 2 of the study the upper BSA restrictions will be removed.
Participant must have confirmation of one of the following diagnosis per St. Jude Children's Research Hospital central pathology review of primary and/or relapsed tumor:
Eligible tumors include:
Low-grade glioma/astrocytic tumor/glioneuronal tumor/neuroepithelial tumor, not otherwise specified (NOS) or not elsewhere classified (NEC)
Pilocytic astrocytoma
Pilomyxoid astrocytoma
Pleomorphic xanthroastrocytoma
Ganglioglioma
Gangliocytoma
Diffuse glioma, diffuse astrocytoma, oligodendroglioma, or oligoastrocytoma
Papillary glioneuronal tumor
Rosette-forming glioneuronal tumor
Diffuse leptomeningeal glioneuronal tumor
Central neurocytoma, extraventricular neurocytoma
Angiocentric glioma
Dysembryoplastic neuroepithelial tumor (DNET), septal DNET, myxoid glioneuronal tumor
Tectal glioma
Desmoplastic infantile astrocytoma / ganglioglioma
Polymorphous low-grade neuroepithelial tumor of the young
Multinodular and vacuolating neuronal tumor
In addition, tumor on central review must show evidence supporting MAPK pathway activation as defined by IHC, FISH and/or DNA/RNA sequencing (i.e. BRAF fused or rearranged, FGFR1/2/3 aberration, NF1, NF2, PTPN11, SOS1, RAF1 mutations, MYB or MYBL1 fused or rearranged, etc.) or occur in a participant with known NF1, NF2, SOS1, RAF1, or PTPN11 germline mutation. (Note: tests that show evidence supporting MAPK pathway activation that have been already performed do not need to be repeated as long as deemed acceptable by central review).
Participant must have measurable or evaluable disease (as defined in the protocol)
Note: Participants with metastatic disease or multiple independent primary LGGs are allowed on study.
Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment with no plans for escalation.
Participant must have a Lansky (\<16 years) or Karnofsky (≥16 years) performance score of ≥ 50 and, in the opinion of the investigator, a minimum life expectancy of at least 6 weeks.
Note: Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Participant must have adequate bone marrow and organ function as defined as:
ANC ≥ 1.0 x 10\^9/L without growth factor support within 7 days
Platelet count ≥ 75x 10\^9/L without support of a platelet transfusion within 7 days
Hemoglobin ≥8.0 g/dL without support of a blood transfusion within 7 days
Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus must be ≤ grade 1 or corrected to ≤ grade 1 with supplements before first dose of study medication
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN. For the purposes of this study the ULN of ALT and AST is 45 U/L.
Total bilirubin ≤ ULN; or if \> ULN then direct bilirubin ≤ 1.5 x ULN
Adequate renal function defined as:
Serum creatinine ≤ the maximum serum creatinine based on age/gender: Age: 2 to \< 6 years: maximum serum creatinine (mg/dL) 0.8 (male, female), Age: 6 to \<10 years: maximum serum creatinine (mg/dL) 1 (male, female), Age: 10 to \<13 years: maximum serum creatinine (mg/dL) 1.2 (male, female), Age: 13 to \<16 years: maximum serum creatinine (mg/dL) 1.5 (male); 1.4 (female), Age: ≥ 16 years: maximum serum creatinine (mg/dL) 1.7 (male); 1.4 (female)
Adequate cardiac function defined as:
LVEF \> 50% by ECHO
QTc interval ≤ 450 msec for male participants, ≤ 470 msec for female participants after electrolytes have been corrected.
Hypertension:
Patients 2-12.99 years of age must have a blood pressure that is ≤ 95th percentile +10 mmHg for age, height, and gender at the time of enrollment (with or without the use of anti-hypertensive medications).
Patients ≥ 13 years of age must have a blood pressure ≤ 140/90 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications).
Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension.
Participants of childbearing/child-fathering potential must agree to use contraception.
Participants and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Participants who are receiving P-gp and BCRP inhibitors must have received their last dose a week or 5 half-lives (whichever is greater) prior to the first mirdametinib dose.
Participant's tumor must have unambiguously progressed, relapsed, or recurred during or after the most recent prior therapy (chemotherapy or radiotherapy) and pseudoprogression or treatment-related tumor changes have, in the opinion of the investigator, been thoroughly vetted.
Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator.
Prior therapy:
Patients who have received the following:
≤ 3 prior treatment regimens with either myelosuppressive chemotherapy or biologic agents and/or
focal radiotherapy
Note that a treatment regimen is defined as a single agent (chemotherapeutic or biologic), or a sequential combination of therapies that can include radiotherapy (with or without concurrent radiosensitizer, chemotherapy, or biologic therapy) followed by maintenance therapy (either single or combination) given over a period of time at either diagnosis or relapse.
Chemotherapy:
Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.
Monoclonal antibody treatment and agents with known prolonged half-lives:
Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment
MEK inhibitors:
Patients must not have received prior exposure to any MEK inhibitors
XRT/External Beam Irradiation including Protons:
Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment
No prior anti-cancer treatment except surgery.
In the opinion of the investigator tumor must warrant treatment defined as any of the following: unsafe to observe, unequivocally progressing on serial imaging, tumor is causing or at high risk of causing neurologic or vision-related deficits.
Participant's tumor must have unambiguously progressed, relapsed, or recurred during or after the most recent prior therapy (chemotherapy or radiotherapy) and pseudoprogression or treatment-related tumor changes have, in the opinion of the investigator, been thoroughly vetted.
Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator.
Prior therapy:
Chemotherapy:
Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.
Monoclonal antibody treatment and agents with known prolonged half-lives:
Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment
MEK inhibitors:
Patients must not have received prior exposure to any MEK inhibitors
XRT/External Beam Irradiation including Protons:
Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment.
Note that for this cohort, there are no limitations on number of prior treatment regimens and participants who have received craniospinal radiation are eligible
Cohort 3A (MEKi responders): Patients who previously received 6 or more cycles of any MEK inhibitor (including mirdametinib) and did NOT progress while on active MEK inhibitor therapy.
The progression must have occurred off MEK inhibitor therapy
Participant's tumor must have unambiguously relapsed or clinically progressed. Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator.
Patient must not have discontinued MEKi (specifically mirdametinib) for unacceptable toxicity, and in the opinion of the PI be able to tolerate subsequent courses of MEKi therapy.
Patients must have received treatment with a MEK inhibitor for ≥6 cycles and showed no signs of progression while on active MEK inhibitor therapy.
Patients who received additional anti-tumor therapy following discontinuation of MEK inhibitor can be enrolled in this cohort.
Prior Therapy:
Chemotherapy:
Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.
Monoclonal antibody treatment and agents with known prolonged half-lives:
Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
MEK inhibitors:
Participant must have received their last dose of MEKi at least 3 weeks prior to study enrollment.
XRT/External Beam Irradiation including Protons:
Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment.
Note that for this cohort, there are no limitations on number of prior treatment regimens and participants who have received craniospinal radiation are eligible
Cohort 3B (MEKi non-responders): Patients with previous exposure to alternative MEK inhibitors (excluding mirdametinib) who progressed while on active MEK inhibitor therapy
Participant's tumor must have unambiguously relapsed or clinically progressed.
Progression may be radiographic or clinical (i.e. vision deterioration thought to be related to tumor in patients with optic pathway tumors, or neurologic deterioration thought to be related to tumor) but it must be unequivocal and sufficient to warrant treatment in the opinion of the investigator. Progression or recurrence must have occurred while on active MEK inhibitor therapy (excluding mirdametinib)
Participants are eligible regardless of how many prior cycles were received or prior history of response (i.e. PR, Major Response, or CR)
Patients who received additional anti-tumor therapy following discontinuation of MEK inhibitor can be enrolled in this cohort as long as they meet the above criteria.
Prior Therapy:
Chemotherapy:
Participant must have received their last dose of myelosuppressive anticancer chemotherapy at least 21 days prior to study enrollment or at least 42 days if nitrosourea.
Monoclonal antibody treatment and agents with known prolonged half-lives:
Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
Alternative MEK inhibitor:
Participant must have received their last dose of MEKi (excluding mirdametinib) at least 3 weeks prior to study enrollment.
XRT/External Beam Irradiation including Protons:
Participant must have had their last fraction of radiation ≥ 3 months prior to study enrollment.
Note that for this cohort, there are no limitations on number of prior treatment regimens and participants who have received craniospinal radiation are eligible.
Exclusion
Participants with known current retinal pathology that is consistent with or a precursor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
Participants with a known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of mirdametinib (e.g., gastric bypass, lap band, or other gastric procedures)
Participant with a known history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones)
Participants with a clinically significant history of chronic interstitial lung disease (such as bronchopulmonary dysplasia, chronic bronchiolitis, obliterative bronchiolitis, chronic aspiration pneumonia, surfactant protein disorder, or other serious chronic pulmonary condition). Participants with a history of asthma, reactive airways disease, or viral pneumonitis are not to be excluded if disease has resolved or is well-controlled.
Participants whose tumor on central review is any of the following:
High-grade (WHO III or IV)
Subependymal giant cell astrocytoma
Ependymoma
Histone H3 K27M/K28M or G34/G35-mutant
BRAF V600 mutant
NTRK1/2/3, ALK, or ROS1 fusion-positive
IDH 1/2 mutant
Participant who is currently receiving any other anticancer or investigational agents (\^11C-methionine allowed) or still recovering from acute toxicity potentially related to the agent.
Ophthalmologic Conditions
Patients with central serous retinopathy
Patients with retinal vein occlusion or retinal detachment
Patients with uncontrolled glaucoma
If checking pressure is clinically indicated and feasible per patient's age and ability to complete exam, patients with IOP \> 22 mmHg or ULN adjusted by age are not eligible
Participants with other clinically significant medical disorders (i.e. serious infections or significant cardiac, pulmonary, hepatic, psychiatric, or other organ dysfunction) that in the investigator's judgement could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results.
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 16 weeks after stopping study therapy are not eligible.
Participants are excluded if unable to comply with protocol guidelines.
What this trial measures
- Phase 1: Estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma.1 month after start of mirdametinib treatment
The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days). We will require that at least 12 DLT evaluable subjects are assessed before the MTD/RP2D is declared.
- Phase 1: Determine the safety and tolerability of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma.Up to 25 months after start of mirdametinib treatment
Incidence of adverse event data at least possibly related to treatment will be summarized in cohort specific tables by grade and attribution throughout treatment.
- Characterize the maximum plasma concentration and area under the concentration-time curve (AUC0-8h) of mirdametinib.Course 1: Days 1 and 15
Mirdametinib plasma concentration will be provided and area under the curve (AUC0-8h) estimated based on course 1, days 1 and 15 PK samples
- Phase 2, Cohort 1: Objective response rate observed anytime during active treatment and sustained for at least 8 weeksUp to 24 months after start of mirdametinib treatment
The response rate, defined as the rate of minor response, partial response (PR), major response, or complete response (CR) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., PR, major response, and CR). Subjects without an assessment will be considered non-responders.
- Phase 2, Cohort 2: Objective response rate observed anytime during active treatment and sustained for at least 8 weeksUp to 24 months after start of mirdametinib treatment
The response rate, defined as the rate of minor response, partial response (PR), major response, or complete response (CR) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., PR, major response, and CR). Subjects without an assessment will be considered non-responders.
- Phase 2, Cohort 3a: Estimate 1-year disease stabilization rateUp to 12 months (slight departures from this timing allowed based on MRI screening) after start of mirdamentinib treatment
Rate of stable disease from start of treatment until the time of progression or time of last follow-up.
- Phase 2, Cohort 3b: Estimate 6-month disease stabilization rateUp to 6 months (slight departures from this timing allowed based on MRI screening) after start of mirdametinib treatment
Rate of stable disease from start of treatment until the time of progression or time of last follow-up.
- Describe the toxicity profile of mirdametinib by cohort.Up to 25 months after start of mirdametinib treatment
Incidence of adverse event data at least possibly related to treatment will be summarized in cohort specific tables by grade and attribution throughout treatment.