HER2-specific Chimeric Antigen Receptor (CAR) T Cells for Children With Ependymoma

NCT04903080 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: PBTC-059UM1CA081457NCI-2021-06710
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 13

Brief Summary

This is a Phase I study to evaluate the safety profile of a type of immune therapy called HER2 CAR T cells (short for HER2 chimeric antigen receptor T cells). In addition to looking for side effects, we will study how well this treatment works against a brain tumor called ependymoma that has come back after treatment (recurrent) or has not responded well to treatment (progressive) in children. The HER2 CAR T cells used in this trial are made from the patient's own blood. A new gene, called the HER2 CAR, will be inserted into patient's T cells to allow them recognize a protein on the tumor called HER2. These HER2-specific CAR T cells may be able to target and kill ependymoma tumors that express HER2. This research is also studying how doable it is to provide this type of CAR T cell treatment to children being treated at different hospitals.

Conditions

Ependymoma

Outcome Measures

Primary Outcomes (3)

• Number of Subjects with Dose-Limiting Toxicity (DLT) in Phase I Arm

  DLT is defined as an adverse event that is at least possibly attributed to the investigational agent (HER2 CAR T cells) that occurs during the dose-finding period (the first 42 days following the first CAR T cell infusion) regardless of expectedness with a few exceptions, for which Section 6.4 of the protocol provides more details. All patients in Safety/Feasibility cohort who received at least 1 dose of HER2 CAR T cells are included in the assessment.

  Up to 42 days following the first CAR T cell infusion

• Number of Subjects with Dose-Limiting Toxicity (DLT) in Surgical Arm

  DLT is defined as an adverse event that is at least possibly attributed to the investigational agent (HER2 CAR T cells) that occurs during the dose-finding period (the first 42 days following the first CAR T cell infusion) regardless of expectedness with a few exceptions, for which Section 6.4 of the protocol provides more details. All patients in Surgical cohort who received at least 1 dose of HER2 CAR T cells are included in the assessment.

  Up to 42 days following the first CAR T cell infusion

• Percentage of Subjects whose Treatment Delivery Meets Feasibility Criteria

  Assessment of feasibility is in the context of conducting an investigator-initiated (not industry sponsored) multi-institutional trial of CAR T cells. This would specifically include the feasibility of manufacturing the cells at one center and shipping them to other sites for administration and the infusion process. If more than 25% of patients cannot be treated as intended due to manufacturing, shipping or administration related causes (jointly considered as feasibility criteria), this would be considered unacceptable. If the treatment is not delivered as intended due to one or more manufacturing, shipping, or administration related causes, this instance will be counted as feasibility failure for that subject.

  Approximately 3 months after enrollment for treatment

Secondary Outcomes (10)

• Expansion and Persistence of HER2 CAR T Cells at First Infusion in patients who received this treatment

  Approximately 3 months after enrollment for treatment

• Expansion and Persistence of HER2 CAR T Cells at Second Infusion in patients who received this treatment

  Approximately 7 months after enrollment of treatment

• Expansion and Persistence of HER2 CAR T Cells at Third Infusion in patients who received this treatment

  Approximately 10 months after enrollment for treatment

• Presence of intra-tumoral HER2 CAR T Cells following First Infusion in Surgical Arm

  Approximately 3 months after enrollment for treatment

• Presence of HER2 CAR T Cells following Second Infusion in Surgical Arm

  Approximately 6 months after enrollment for treatment

Study Arms (2)

Treatment (HER2 CAR T cells), Phase I Arm

EXPERIMENTAL

Patients receive lymphodepletion chemotherapy with cyclophosphamide IV daily on Days -7 to -6 and fludarabine IV daily on Days -5 to -1. Patients receive HER2 CAR T cells IV on Day 0. Treatment repeats every 8 to 12 weeks for 2 additional cycles in the absence of disease progression or unacceptable toxicity.

Biological: HER2 Specific CAR T Cell

Treatment (HER2 CAR T cells), Surgical Arm

EXPERIMENTAL

Patients receive lymphodepletion chemotherapy with cyclophosphamide IV daily on Days -7 to -6 and fludarabine IV daily on Days -5 to -1. Patients receive HER2 CAR T cells IV on Day 0 followed by surgical tumor resection 4-6 weeks following HER2 CAR T cell infusion. Treatment repeats every 8 to 15 weeks for 2 additional cycles in the absence of disease progression or unacceptable toxicity.

Biological: HER2 Specific CAR T Cell

Interventions

HER2 Specific CAR T Cell BIOLOGICAL

HER2 CAR (Chimeric Antigen Receptor) T cells are T cells that have been genetically engineered to target the protein HER2 for the treatment of cancer.

Treatment (HER2 CAR T cells), Phase I Arm; Treatment (HER2 CAR T cells), Surgical Arm

Eligibility Criteria

• Age: 1 Year - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Tumor
• Patient must have been screened and determined to have a diagnosis of a HER2-positive recurrent or progressive ependymoma.
• Performance Score
• Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) (Appendix C) assessed within one week of procurement must be ≥ 60%. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score provided the neurological deficit is stable as described in Section 3.3.1.7.
• Prior Therapy
• Patients must have received last dose of cytotoxic chemotherapy greater than 21 days preceding the date of enrollment for procurement.
• Organ Function
• Patient must have adequate organ and bone marrow function as defined below:
• Peripheral absolute neutrophil count (ANC) \> 1.0 x 109 cells/L
• Platelet count ≥ 75 100 x 109 cells/L (unsupported, defined as no platelet transfusion within 4 days)
• Hemoglobin ≥ 8 g/dL (may receive red blood cell transfusions)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) for age
• Alanine transaminase (ALT /SGPT) and Aspartate aminotransferase(AST/SGOT) ≤ 3 x institutional upper limit of normal (ULN) for age
• Serum creatinine \< 1.5 x institutional upper limit of normal for age and gender. Patients that do not meet the criteria but have a 24-hour Creatinine Clearance or Glomerular filtration rate (GFR) (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2 are eligible.
• Pulmonary Function

You may not qualify if:

• \. Known HIV Positivity
• Patients who are known to be HIV-positive are ineligible due to the unknown safety and efficacy of infusing these patients with CAR T cells genetically modified using retroviral vectors. Additionally, the immunosuppression used for treatment in this study will pose an unacceptable risk.
• Criteria for Treatment
• Diagnosis
• Patients with a histologically confirmed diagnosis of HER2 positive ependymoma that is recurrent or progressive. Histologic verification may be from time of diagnosis or time of recurrence. In cases where there is question of recurrence, histologic verification, or verification of progression on follow up imaging is required prior to enrolling for protocol treatment.
• Disease Status
• Phase I (Stratum 1) - Patients must have evaluable disease to be eligible. Evaluable disease includes either measurable OR non-measurable disease, defined as follows:
• Measurable disease (enhancing or non-enhancing tumor):
• at least 1 cm, or
• at least two times (in both perpendicular diameters) the MRI slice thickness, plus the interslice gap.
• Non-measurable disease (tumor that is too small to be accurately measured):
• less than 1 cm in at least one perpendicular dimension, or
• less than two times the MRI slice thickness, plus the interslice gap.
• Note: Leptomeningeal disease is considered non-measurable but evaluable.
• Surgical Study (Stratum 2) - Patients with measurable disease (Section 3.3.1.2.1) in whom tumor resection is clinically indicated and feasible after the CAR T cell infusion.

Sponsors & Collaborators

• Children's Oncology Group: lead
• Texas Children's Cancer Center: collaborator
• Baylor College of Medicine: collaborator
• National Cancer Institute (NCI): collaborator
• American Lebanese Syrian Associated Charities: collaborator
• Pediatric Brain Tumor Consortium: collaborator

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90026, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

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

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Pittsburgh Children's Hospital of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

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

Study Officials

• Meenakshi Hegde, MD

  Baylor College of Medicine

  STUDY CHAIR

Study Design

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

Model Details: This study includes two groups: a safety cohort and a surgical cohort.

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 26, 2021
• Study Start: July 27, 2022
• Primary Completion: March 31, 2026
• Study Completion (Estimated): July 20, 2043
• Last Updated: March 5, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (12)