ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas

NCT06838676 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CONNECT2110
• Study Type: interventional
• Target: 60
• Locations: 5 countries
• Sites: 20

Brief 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.

Conditions

Progressive DIPG; Refractory DIPG; Recurrent DIPG; H3K27-altered High Grade Glioma; Diffuse Intrinsic Pontine Gliomas (DIPG)

Keywords

High Grade Glioma; Diffuse Intrinsic Pontine Glioma

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS) for newly diagnosed DIPG

  To assess the overall survival for newly-diagnosed patients with DIPG treated with RT followed by ACT001.

  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

  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

  From date on treatment until date of death due to any cause or date of last follow-up, assessed up to 60 months

Study Arms (2)

Cohort A

EXPERIMENTAL

Patients with newly-diagnosed DIPG with typical MRI findings

Drug: ACT001

Cohort B

EXPERIMENTAL

Patients with progressive/refractory/recurrent DIPG or extra-pontine H3K27-altered HGG tumors that have progressed following frontline treatment

Drug: ACT001

Interventions

ACT001 DRUG

PO BID at 875 mg/m2 for 28 days

Cohort A; Cohort B

Eligibility Criteria

• Age: 12 Months - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 of radiographic diagnosis (for non-biopsied DIPG patients only) or definitive surgery, whichever is later. It is strongly recommended patients begin RT within 31 days of diagnosis/definitive surgery.
• 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)
• Patients must have received RT, but no other anti-cancer therapy other than surgery, and/or steroids prior to enrollment.
• Cohort B: progressive/refractory/recurrent DIPG or H3K27-altered HGG
• Patients with DIPG (no biopsy required) or pathologically-confirmed (at diagnosis or recurrence) extra-pontine H3K27-altered HGG who have progressive, refractory or recurrent disease following frontline treatment that included at least focal RT. Patients with refractory disease must have completed RT \>6 months prior to study enrollment.
• Patients with progressive disease only at the primary site(s) must have completed RT more than 3 months prior to enrollment.
• Patients with progressive disease only at the primary site(s) who completed radiation therapy 3 to 6 months prior to enrollment must have had at least one follow up MRI to confirm progression (rather than pseudo- progression)
• Patients with progressive disease due to the development a new metastatic site are eligible as long as eligibility criteria 3 (disease status) and 5 (prior RT) are met.
• 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.

You may not qualify if:

• The wash out period between the prior anti-cancer chemotherapy, and first dose of ACT001 (cycle 1 day 1) 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 and toxicity related to antibody therapy must be recovered to Grade ≤ 1
• Radiation therapy:
• For Cohort B, patients with refractory disease must have received their last fraction of frontline craniospinal or focal RT \> 6 months prior to study enrollment. Patients that have received re-irradiation for progression must have received their last fraction of focal radiation \>6 weeks or craniospinal radiation \>6 weeks 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

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• Accendatech USA Inc.: collaborator

Study Sites (20)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

NOT YET RECRUITING

Emory University/Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

NOT YET RECRUITING

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

NOT YET RECRUITING

Duke University Medical Center

Durham, North Carolina, 27708, United States

NOT YET RECRUITING

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43235, United States

RECRUITING

Children's Hospital of Philidelphia

Philidelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

NOT YET RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

NOT YET RECRUITING

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

NOT YET RECRUITING

Perth Children's Hospital

Perth, Western Australia, 6000, Australia

NOT YET RECRUITING

The Hospital for Sick Children (SickKids)

Toronto, Ontario, M5G1X8, Canada

NOT YET RECRUITING

Montreal Children's Hospital

Montreal, Quebec, H4A3J1, Canada

NOT YET RECRUITING

Hopp Children's Cancer Center at NCT Heidelberg (KiTZ)

Heidelberg, Baden-Wurttemberg, 69120, Germany

NOT YET RECRUITING

Starship Children's Hospital

Auckland, Grafton, 1023, New Zealand

NOT YET RECRUITING

MeSH Terms

Conditions

Glioma; Diffuse Intrinsic Pontine Glioma

Interventions

ACT001

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• David S. Ziegler, MD, FRACP

  Sydney Children's Hospitals Network

  STUDY CHAIR

• Sara Khan, MD, PhD, FRACP

  Nationwide Children's Hospital

  STUDY CHAIR

• Peter de Blank, MD, MSCE

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Central Study Contacts

Kelsey H Troyer, PhD

CONTACT

16147223284; kelsey.troyer@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: ACT001

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 21, 2025
• Study Start: July 10, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2035
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); NZ (1); DE (1); US (12); AU (4)