NCT06838676
ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas
Recruiting
PHASE2Ages 12–39InterventionalTreatmentNationwide Children's HospitalInvestigator-initiated
~60 participants
Updated 2026-08-12 on ClinicalTrials.gov
What's tested:ACT001
At a glance
Recruiting sites
8 of 20 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall Survival (OS) for newly diagnosed DIPG
Measured over From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
+1 more outcome measured
Conditions
Where it's being run
20 sites across 19 statesOhio2
Colorado1
District of Columbia1
Florida1
Georgia1
Michigan1
Missouri1
North Carolina1
Study leadership
- David S. Ziegler, MD, FRACP · STUDY_CHAIR · Sydney Children's Hospitals Network
- Sara Khan, MD, PhD, FRACP · STUDY_CHAIR · Nationwide Children's Hospital
- Peter de Blank, MD, MSCE · STUDY_CHAIR · Children's Hospital Medical Center, Cincinnati
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Cohort A: Newly Diagnosed DIPG
Patients with newly-diagnosed DIPG with typical MRI findings (tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons) with or without biopsy and have completed radiation therapy (RT) within 28 to 35 calendar day prior to start of therapy.
Patients must have started RT \<42 calendar days from radiographic diagnosis (for non-biopsied DIPG patients only) or definitive surgery, whichever is later.
If a biopsy was performed, the date of surgical biopsy will be considered the date of definitive diagnostic surgery; if a patient underwent two upfront surgeries \[e.g., biopsy then debulking\], this is the date of the second surgery)
Cohort B: progressive/recurrent DIPG or H3K27-altered HGG OR refractory disease
Patients with DIPG (no biopsy required), pathologically-confirmed (at diagnosis or recurrence) H3K27-altered DIPG, or extra-pontine H3K27-alteredHGG who have progressive/recurrent or refractory disease
Progressive/recurrent: patients who have progressive or recurrent disease following frontline treatment must have included at least focal RT. New lesions since completion of frontline RT qualify as progressive disease.
Refractory disease is defined as: Presence of persistent, measurable, abnormality on conventional MRI that is further distinguished by histology or advanced imaging, OR as determined by the treating physician and discussed with the Study Chair(s) prior to enrollment.
Patients with H3K27-altered spinal HGG are eligible.
Patients with metastatic disease are eligible. 3. Disease Status
Cohort A: patients may have any disease status but must have completed initial radiation therapy (RT) before enrollment.
Cohort B: Patients must have measurable disease assessable by MRI. Patients may have extra neuronal disease. 4. Performance Level: Karnofsky Performance Scale score ≥ 50% for patients \> 16 years of age and Lansky Performance Scale score \> 50% for patients ≤ 16 years of age (applies to all patients) Note: Patients who are unable to walk because of paralysis, but who are capable of using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 5. Prior anti-cancer therapy:
For Cohort A ONLY:
Surgery, radiation (focal to disease) and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy) are permissible. Temozolomide administered concurrently with RT is permissible. Bevacizumab use is permitted given the last dose was administered \>/= 21 days prior to enrollment. No other prior anticancer therapy for DIPG will be allowed.
Patients must enroll and start treatment on study between 28 and 35 calendar days post-completion of RT.
Patients must have started RT \<42 calendar days of initial diagnosis (defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries \[e.g., biopsy then resection or debulking\], this is the date of the second surgery).
Radiotherapy must have been administered at standard dose of 54 Gy for DIPG patients. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment.
For Cohort B ONLY: Patients must have fully recovered from the acute treatment related toxicities (defined as \</= Grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering on this study, with the exception of alopecia.
Cohort A - Patients that have received any anti-cancer treatment other than surgery, RT, temozolomide concurrent with RT, and/or previous bevacizumab with appropriate washout period are not eligible.
Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible.
Anticonvulsants should be used as clinically indicated. The use of enzyme inducing anticonvulsants is not permitted
LHRH agonist / antagonists are not permitted
High Dose Biotin (B7) supplements are not permitted 3. Concomitant medications used with caution: selective serotonin reuptake inhibitor (SSRI) such as Lexapro, Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and escitalopram should be used with caution. 4. Infection: Patients who currently have an uncontrolled infection (in the opinion of the PI) are not eligible. 5. Patients who have received a prior solid organ transplantation are not eligible. 6. Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are postmenarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. 7. Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods (hormonal or barrier method of birth control; abstinence) while being treated on this study and for 3 months after completing therapy. Note: The definition of effective contraception will be based on the judgement of the principal investigator or a designated associate. 8. Patients who are in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. 9. Patients who have previously received either ACT001 or parthenolide are not eligible.
Exclusion
All Cohort B patients: Patients must have received their last fraction of focal irradiation to new sites of progressive disease \> 14 days prior to enrollment.
Patients who received CSI must have received their last fraction \> 3 months prior to enrollment.
Progressive/recurrent disease: Patients who received re-irradiation to primary disease must have received their last fraction \> 3 months prior to study enrollment.
Refractory Disease:
Patients must have completed frontline RT \> 6 months prior to enrollment.
Patients who received re-irradiation to primary disease must have received their last fraction \> 3 months prior to study enrollment. 7. Stem Cell Transplant: Patients must be ≥ 3 months since autologous stem cell transplant. Patients who received allogenic stem cell transplant or solid organ transplant are not eligible for study 6. Organ Function Requirements (applies to all patients)
Peripheral absolute neutrophil count (ANC) \> 1000/mm³
Platelet count \> 100,000/mm³ (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) 2. Adequate renal function defined as:
Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m² or
A serum creatinine based on age/gender as follows (Schwartz et al. J. Peds, 106:522, 1985): Age Maximum Serum Creatinine (mg/dL) Male Female 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1.0 1.0 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 ≥ 16 years 1.7 1.4 3. Adequate liver function defined as:
total bilirubin must be \</=1.5X institutional ULN for age
AST (serum glutamic-oxaloacetic transaminase \[SGOT\]) / ALT (serum glutamic-oxaloacetic transaminase \[SGPT\]) ≤ 2.5 × institutional upper limit of normal
Serum albumin ≥ 2 g/dL 4. Adequate cardiac function defined as:
Ejection fraction of ≥ 50% by echocardiogram
QTc ≤ 450 msec (by Bazett formula) 5. For Cohort B: Adequate neurologic function defined as:
Patients with seizure disorders may be enrolled if seizures are well- controlled. Well controlled is defined by no increase in seizure frequency in the 7 days prior to enrollment.
Patients with neurological deficits should have deficits that are stable for at least the 7 days prior to enrollment. 7. Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. 8. Absence of other clinically significant concomitant active medical disorder, based on the investigator's judgement.
Corticosteroids:
Cohort A - Patients receiving corticosteroids are eligible regardless of dosing
Cohort B - Patients receiving corticosteroids who have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are eligible
What this trial measures
- Overall Survival (OS) for newly diagnosed DIPGFrom date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
To assess the overall survival for newly-diagnosed patients with DIPG treated with RT followed by ACT001.
- Objective Response Rate (ORR) in Progressive/Refractory/Recurrent HGG after frontline RTDate on treatment through 30 days following end of protocol treatment
To assess the rate of objective response rate (defined as partial response + complete response) in patients who have been treated with at least frontline focal RT and have progressive DIPG or progressive/recurrent/refractory H3K27-altered HGG who are treated with ACT001