Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)

NCT06193759 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IMPACT
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label phase 1 safety and feasibility study that will employ multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) derived from a patient's primary brain tumor tissues. Young patients with embryonal central nervous system (CNS) malignancies typically are unable to receive irradiation due to significant adverse effects and are treated with intensive chemotherapy followed by autologous stem cell rescue; however, despite intensive therapy, many of these patients relapse. In this study, individualized TSA-T cells will be generated against proteogenomically determined tumor-specific antigens after standard of care treatment in children less than 5 years of age with embryonal brain tumors. Correlative biological studies will measure clinical anti-tumor, immunological and biomarker effects.

Conditions

Medulloblastoma, Childhood; Atypical Teratoid/Rhabdoid Tumor of CNS; Pineoblastoma; Embryonal Brain Tumor Not Otherwise Specified; Embryonal Tumor With Multilayered Rosettes; Ependymoma

Keywords

Cellular Therapy; Pediatric Brain Tumors

Outcome Measures

Primary Outcomes (4)

• To evaluate the safety of TSA-T in children, adolescents, and young adults with high-risk CNS embryonal tumors and recurrent ependymomas. Safety will be evaluated by the incidence of dose limiting toxicities (DLTs).

  The safety endpoint will be assessed by monitoring for incidence of DLTs-defined as any of the below events occurring within 42 days following a participant's first TSA-T infusion (per CTCAE v. 6.0): * Grade ≥3 infusion-related adverse event. * Grade ≥4 non-hematologic adverse event that is not due to the patient's underlying malignancy or chemotherapy related co-morbidities. * Grade ≥3 pneumonitis, uveitis. * Grade ≥3 toxicities that are attributed to TSA-T (possibly, probably or definitely TSA-T related). * Unexpected toxicity of grade ≥3 attributed to the infusion of TSA-T (possibly, probably or definitely TSA-T related).

  42 days of the first TSA-T infusion

• To estimate the maximum-tolerated dose (MTD) of intracerebroventricularly-administered TSA-T in children, adolescents and young adults with high-risk CNS embryonal tumors and recurrent ependymoma.

  The MTD will be estimated adaptively throughout the trial using Bayesian optimal interval (BOIN) design, based on incidence of DLTs. After trial completion, the final maximum tolerated dose regimen (MTDR) will be selected using isotonic regression of pooled safety data from Groups A and B.

  42 days of the first TSA-T infusion

• Feasibility of TSA identification

  The number of TSA identified for each tumor will be measured. The endpoint will be the number of patients with at least 2 TSA peptides identified.

  Up to 5 years after the first TSA-T cell infusion

• Feasibility of TSA-T cell generation

  The time from the acquisition of tissue to the availability of manufactured TSA-T products, measured in comparison to the length of the SOC therapy regimen/s preceding the infusion (\~12-24 weeks).

  At start of SOC/Salvage therapy until start of TSA-T cell treatment (up to 24 weeks)

Secondary Outcomes (5)

• To record preliminary evidence of objective disease response to TSA-T cells in embryonal tumors and recurrent ependymomas, among patients with residual disease after completion of SOC or salvage treatment per protocol

  Up to 1 year after first TSA-T cell infusion

• To record preliminary evidence of prolonged survival through analysis of progression free survival (PFS) and overall survival (OS).

  Up to 5 years after the first TSA-T cell infusion

• To correlate clinical parameters (objective disease response, survival, and adverse events) with in vivo persistence of TSA-T and other measures of immune response in cerebrospinal fluid (CSF).

  Up to 5 years after the first TSA-T cell infusion

• To characterize the phenotype of manufactured TSA-T cells prior to infusion and correlate with clinical parameters.

  After TSA-T cell manufacturing up to infusion of TSA-T cells (up to 24 weeks)

• To characterize specificity of manufactured TSA-T cells prior to infusion and correlate with clinical parameters

  After TSA-T cell manufacturing up to infusion of TSA-T cells (up to 24 weeks)

Study Arms (2)

Embryonal brain tumors

EXPERIMENTAL

Children younger than 5 years of age with newly diagnosed embryonal brain tumors - including medulloblastoma (MB), atypical teratoid/rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and embryonal brain tumor not otherwise specified (NOS).

Biological: Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA); Drug: Group A Standard-of-Care Backbone Therapy

Ependymoma

EXPERIMENTAL

Children, adolescents and young adults greater than 1 year and less than 30 years of age with recurrent ependymoma

Biological: Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA); Radiation: Group B Salvage Backbone Therapy

Interventions

Group A Standard-of-Care Backbone Therapy DRUG

Patients will undergo surgical resection, then be treated with standard-of-care therapy as required, which may include up to 3 induction chemotherapy cycles (vincristine, cyclophosphamide, cisplatin, etoposide with or without methotrexate) and up to 3 consolidation cycles (carboplatin and thiotepa, each followed by an infusion of autologous peripheral blood stem cells).

Embryonal brain tumors

Group B Salvage Backbone Therapy RADIATION

Patients will undergo surgical re-resection - aiming for gross total resection when feasible - followed by re-irradiation. Re-irradiation may be delivered as a conventional fractionated course, hypofractionated stereotactic radiotherapy, or proton therapy.

Ependymoma

Multi-tumor antigen specific cytotoxic T lymphocytes (TSA-T) directed against proteogenomically determined personalized tumor-specific antigens (TSA) BIOLOGICAL

Participants in this study will receive TSA-T after completion of standard-of-care treatment.

Embryonal brain tumors; Ependymoma

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis (select one group):
• Group A: New diagnosis of CNS embryonal tumors: medulloblastoma, embryonal tumor with multilayered rosettes, pineoblastoma, atypical teratoid/rhabdoid tumor, and embryonal tumor, not otherwise specified (NOS).
• Group B: Radiographic evidence consistent with recurrent ependymoma, with planned or recent re-resection.
• Age:
• Group A: \<5 years of age at enrollment
• Group B: \>1 year and \<30 years of age at enrollment
• Tissue:
• o Group A: Availability of sufficient fresh or frozen tumor tissue (approximately 50 mg).
• o Group B: Expectation of sufficient fresh or frozen tumor tissue, in the opinion of study PI or sub-I (based upon radiographic evidence of disease).
• Non-pregnant:
• Group A: N/A
• Group B: For female of childbearing potential, must have negative pregnancy test.
• Common to both groups:
• Karnofsky or Lansky score of ≥60%.
• Adequate organ function, defined below:

You may not qualify if:

• \. Patients with uncontrolled infections. 2. Patients with known HIV infection. 3. Group A patients with medulloblastoma of the SHH subtype.
• \. Patients with a fever above 38.0°C. 2. Patients with known HIV infection. 3. Prior immunotherapy with an investigational agent within the 28 days prior to planned date of procurement collection for TSA-T manufacturing.
• \. Patients who will be unable to tolerate the apheresis procedure, including inability to tolerate placement of apheresis line (if applicable), in the opinion of PI or medically licensed sub-I.
• \. Patients who have overly bulky tumors on imaging are ineligible. These include the following: i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.
• Patients with progressive disease based on most recent evaluation (for subsequent infusions).
• a. Patients with progressive disease based on most recent evaluation may receive initial TSA-T infusion but would be ineligible if the tumor is found to be progressive before subsequent infusions
• Patients with uncontrolled infections.
• Patients who have overly bulky tumors on imaging are ineligible. These include the following:
• i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study.
• Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of TSA-T infusion.
• Patients receiving steroids (e.g., dexamethasone) at a dose of \>0.05 mg/kg/day.
• Patients who have non-programmable VP shunts.

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Hospital

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

RECRUITING

MeSH Terms

Conditions

Medulloblastoma; Rhabdoid Tumor; Neuroectodermal Tumors, Primitive; Pinealoma; Ependymoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Brian Rood, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brian Rood, MD

CONTACT

2024762314; BROOD@childrensnational.org

Fahmida Hoq, MBBS

CONTACT

2024763634; FHOQ@childrensnational.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2023
• First Posted: January 5, 2024
• Study Start: September 20, 2024
• Primary Completion (Estimated): December 29, 2030
• Study Completion (Estimated): December 29, 2032
• Last Updated: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)