Diffuse Intrinsic Pontine Gliomas (DIPG)Phase 2NCT06838676
ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas
A Phase 2 study testing ACT001 in people with Diffuse Intrinsic Pontine Gliomas (DIPG) and Progressive DIPG, run by Nationwide Children's Hospital at 20 sites in 5 countries.
Trial summary
This is a Phase II open-label study to investigate the safety and efficacy of ACT001 in patients with DIPG and H3K27-altered HGG. Read more about this study
- Who is it for?
- Ages 12 months to 39 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Gliomas (DIPG), Progressive DIPG, Refractory DIPG
- What is being tested?
- ACT001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 20 sitesin 5 countries
- Study dates
- 10 Jul 2025to Jul 2035
- Phase
- Phase 2
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 months to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
- Diagnosis:
- 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)
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- Cohort B [ENROLLMENT PAUSED]: 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.
- 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.
- 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.
- 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.
- Notes to the above for Cohort B: Patients with chronic Grade 2 toxicities may be eligible per discretion of the Investigator and Sponsor (e.g., Grade 2 chemotherapy-induced neuropathy). Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible - defined as having been present and stable for > 6 months (such as ifosfamide-related proteinuria) may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the Investigator and Sponsor.)
- The wash out period between the prior anti-cancer chemotherapy, and enrollment must be:
- Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
- Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
- Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
- Monoclonal antibodies: > 21 days must have elapsed from the infusion of last dose of antibody
- Radiation therapy:
- 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.
- 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
- Organ Function Requirements (applies to all patients)
- Adequate bone marrow function defined as:
- 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)
- 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
- 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
- Adequate cardiac function defined as:
- Ejection fraction of ≥ 50% by echocardiogram
- QTc ≤ 450 msec (by Bazett formula)
- 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.
- 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.
- Absence of other clinically significant concomitant active medical disorder, based on the investigator's judgement.
Who cannot join
- A patient who meets any of the following exclusion criteria will not be eligible in the study (Applies to both cohorts except where noted below):
- Cohort A only: Patients with metastatic disease.
- Concomitant medications:
- 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
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- Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible (Refer study inclusion criteria relating to anti-cancer therapies)
- 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
- 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.
- Infection: Patients who currently have an uncontrolled infection (in the opinion of the PI) are not eligible.
- Patients who have received a prior solid organ transplantation are not eligible.
- 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.
- 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.
- 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.
- Patients who have previously received either ACT001 or parthenolide are not eligible.
Trial locations and contacts
20 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
20 sites in 5 countries
United States12 sites, 12 recruiting
- Recruiting
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109
Santhosh Upadhyaya, MBBS, 734-647-8902, saupadhy@med.umich.edu
Carl Koschmann, MD, 734-647-8902, ckoschma@med.umich.edu
- Not yet recruiting
Emory University/Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Tobey MacDonald, MD, 404-785-1112, tobey.macdonald@emory.edu
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Holly Lindsay, MD, 720-777-6740, holly.lindsay@childrenscolorado.org
- Recruiting
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Peter de Blank, MD, 513-517-2068, Peter.deBlank@cchmc.org
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43235
Sara Khan, MD, 614-722-5758, Sara.Khan@nationwidechildrens.org
- Not yet recruiting
Duke University Medical Center
Durham, North Carolina, 27708
Daniel Landi, MD, 919-684-2410, daniel.landi@duke.edu
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Patricia Baxter, MD, 832-824-4681, pabaxter@txch.org
- Not yet recruiting
Nicklaus Children's Hospital
Miami, Florida, 33155
Ziad Khatib, MD, 305-662-8360, ziad.khatib@nicklaushealth.org
- Not yet recruiting
Children's Hospital of Philidelphia
Philidelphia, Pennsylvania, 19104
MIchael J Fisher, MD, 215-590-5188, fisherm@email.chop.edu
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Erin Crotty, MD, 206-987-2106, erin.crotty@seattlechildrens.org
- Not yet recruiting
St. Louis Children's Hospital
St Louis, Missouri, 63110
Eric Thompson, MD, 314-454-2810, t.eric@wustl.edu
Mohamed Abdelbaki, MD, mohameda@wustl.edu
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Eugene Hwang, MD, 202-476-5046, ehwang@childrensnational.org
Australia4 sites, 4 recruiting
- Not yet recruiting
Royal Children's Hospital
Melbourne, Victoria, 3052
David Eisenstat, MD, david.eisenstat@rch.org.au
- Not yet recruiting
Perth Children's Hospital
Perth, Western Australia, 6000
Nick Gottardo, MBChB, FRACP, PhD, 618 6456 0241, nick.gottardo@health.wa.gov.au
- Recruiting
Sydney Children's Hospital
Randwick, New South Wales, 2031
David Ziegler, MBBS, BSc, MD, PhD, FRACP, 612 9382 1730, d.ziegler@unsw.edu.au
- Not yet recruiting
Queensland Children's Hospital
South Brisbane, Queensland, 4101
Tim Hassall, MBBS, 61 7 3068 3593, tim.hassall@health.qld.gov.au
Canada2 sites, 2 recruiting
- Not yet recruiting
Montreal Children's Hospital
Montreal, Quebec, H4A3J1
Genevieve Legault, MD, 514-412-4400 ext. 60497, Genevieve.Legault4@mcgill.ca
- Recruiting
The Hospital for Sick Children (SickKids)
Toronto, Ontario, M5G1X8
Anirban Das, MD, 416-813-7654 ext. 429907, anirban.das@sickkids.ca
Germany1 site, 1 recruiting
- Not yet recruiting
Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)
Heidelberg, Baden-Wurttemberg, 69120
Olaf Witt, MD, 49 6221 42 3570, o.witt@kitz-heidelberg.de
New Zealand1 site, 1 recruiting
- Not yet recruiting
Starship Children's Hospital
Auckland, Grafton, 1023
Sarah Hunter, MB ChB, +64 9 367 0000, SHunter@adhb.govt.nz
About this study
Official title: A Phase II Trial of ACT001 in Children and Adolescents With Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas
This is a Phase II open-label study to investigate the safety and efficacy of ACT001 in patients with DIPG and H3K27-altered HGG.
Read the detailed description
Patients will be enrolled on either Cohort A for newly diagnosed DIPG or on Cohort B [ENROLLMENT PAUSED] for those with progressive / refractory DIPG or progressive / recurrent / refractory H3K27-altered HGG. Each cohort will receive ACT001 at 875 mg/m2 orally BID for 28 days (1 cycle of treatment), up to a maximum dose of 1700 mg BID. If patients are experiencing clinical benefit from study therapy, they will continue to receive ACT001 in repeat 28-day cycles for up to 26 cycles (approximately 2 years) or until disease progression, whichever occurs first. Continuation of treatment beyond 26 cycles may be considered if patients are receiving clinical benefit from the study, at the discretion of the sponsor and treating physician.
- Conditions
- Diffuse Intrinsic Pontine Gliomas (DIPG), Progressive DIPG, Refractory DIPG, Recurrent DIPG, H3K27-altered High Grade Glioma
- Being tested
- ACT001
- Keywords
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACT001Drug
PO BID at 875 mg/m2 for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Patients with newly-diagnosed DIPG with typical MRI findings Receives: Drug: ACT001 |
| Cohort B [ENROLLMENT PAUSED] | Experimental | Patients with progressive/recurrent DIPG or H3K27-altered HGG OR refractory disease Receives: Drug: ACT001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) for newly diagnosed DIPG
To assess the overall survival for newly-diagnosed patients with DIPG treated with RT followed by ACT001.
Measured: From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
Objective Response Rate (ORR) in Progressive/Refractory/Recurrent HGG after frontline RT
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
Measured: Date on treatment through 30 days following end of protocol treatment
Secondary outcomes (1)
Overall Survival in Progressive/Refractory/Recurrent DIPG and H3K27-altered DIPG
To estimate the overall survival and duration of disease control for patients who have been treated with at least RT and have progressive DIPG or progressive/recurrent/refractory H3K27-altered HGG who are treated with ACT001
Measured: From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2025
- Study start10 Jul 2025
- Primary completionJul 2028 (estimated)
- Study completionJul 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine Gliomas (DIPG)Studies of the same condition, open and under way.
- 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
- Single group
- Model description
- ACT001
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Accendatech USA Inc.
- Responsible party
- Sponsor
- Investigators
- David S. Ziegler, MD, FRACP, Study chair, Sydney Children's Hospitals NetworkSara Khan, MD, PhD, FRACP, Study chair, Nationwide Children's HospitalPeter de Blank, MD, MSCE, Study chair, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06838676
- Sponsor's protocol ID
- CONNECT2110
- Status last verified
- May 2026
- First submitted
- 19 Feb 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No