T Cells Expressing HER2-specific Chimeric Antigen Receptors(CAR) for Patients With HER2-Positive CNS Tumors

NCT02442297 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: H-31973-iCAR
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This study is for patients that have brain cancer. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting immune cells present in the blood that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to tumor cells because of a substance on the outside of these cells called HER2. Many types of brain tumors are positive for HER2 . HER2 antibodies have been used to treat people with HER2-positive cancers. For this study, the HER2 antibody has been changed so that instead of floating free in the blood it is now attached to T cells. When an antibody is joined to a T cell in this way it is called a chimeric antigen receptor (CAR). These CAR-T cells seem to be able to kill tumors like the one these patients have, but they don't last very long and so their chances of fighting the cancer are limited. Therefore, developing ways to prolong the life of these T cells should help them fight cancer. These HER2-CAR T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the largest safe dose of HER2-CAR T cells, to learn what the side effects are, and to see whether this experimental intervention might help patients with brain tumors who volunteer to test this new agent.

Conditions

Brain Tumor, Recurrent; Brain Tumor, Refractory

Keywords

CNS Tumors; T cells Expressing HER2-specific Chimeric Antigen Receptors; HER2-specific T cells; intracranial injection

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicity after administration of autologous T cells expressing transgenic chimeric antigen receptors (CAR) targeting the HER2 molecule

  To evaluate the safety of autologous T cells expressing transgenic chimeric antigen receptors (CAR) targeting the HER2 molecule administered into the tumor, tumor resection cavity, and/or cerebrospinal fluid (CSF) space of subjects with progressive recurrent or refractory HER2-positive primary central nervous system (CNS) tumor or HER2 positive tumor metastatic to the CNS, excluding diffuse intrapontine glioma (DIPG), after standard of care interventions.

  6 weeks

Secondary Outcomes (1)

• Number of Patients with a tumor response

  6 weeks

Study Arms (2)

HER2-specific T cells - High Risk

EXPERIMENTAL

Subjects with HER2 staining of Grade 3 (51-100% of cells staining for HER2) and intensity scores of 3+ will be assigned to the High Risk arm. Three cell dosing schedules (1, 2, 3) consisting of combinations of three cell doses (A, B, C) will be evaluated.

Biological: HER2-specific T cells

HER2-specific T cells - Standard Risk

EXPERIMENTAL

All other patients not meeting the high risk description will be assigned to the Standard Risk arm. Three cell dosing schedules (1, 2, 3) consisting of combinations of three cell doses (A, B, C) will be evaluated.

Biological: HER2-specific T cells

Interventions

HER2-specific T cells BIOLOGICAL

Dosing Schedule 1: Cycle 1 A: 1x10\^7 cells Cycle 2 A: 1x10\^7 cells Cycle 3 A: 1x10\^7 cells Dosing Schedule 2: Cycle 1 A: 1x10\^7 cells Cycle 2 B: 3x10\^7 cells Cycle 3 B: 3x10\^7 cells Dosing Schedule 3: Cycle 1 A: 1x10\^7 cells Cycle 2 B: 3x10\^7 cells Cycle 3 C: 1x10\^8 cells Subsequent cycles\* \*Additional cycles may be administered at ≤ the final cell dose reached in cycle 3, provided that the subject continues to meet eligibility criteria and does not have confirmed progressive disease.

Also known as: Dosing Schedules 1, 2, and 3

HER2-specific T cells - High Risk; HER2-specific T cells - Standard Risk

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent or refractory HER2 positive primary central nervous system (CNS) tumor or HER2 positive tumor metastatic to the CNS. Patients in whom tumor resection (gross total or subtotal resection) is medically feasible can undergo surgery after procurement and prior to treatment.
• Karnofsky/Lansky score of greater than or equal to 60
• Informed consent explained to, understood by and signed by subject/guardian. Subject/guardian given copy of informed consent

You may not qualify if:

• Diagnosis of DIPG
• Bulky tumors causing midline shift and/or symptoms/signs due to impending herniation
• Known HIV positivity
• Recurrent or refractory HER2-positive\* primary CNS tumor or HER2-positive solid tumor metastatic to the CNS
• \* Immunohistochemistry (IHC) or RT-PCR will be used to determine HER2 positivity. Results will be compared to standard controls. HER2 expression in tumors on IHC should be greater than or equal to grade 1 and greater than or equal to 1+ intensity score. Wherein grades are defined as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-75% and Grade 4: 76-100% of cell staining for HER2 and intensity scores are: negative; 1+; 2+ and 3+ using breast cancer standard arrays as a guide for intensity.
• Intracranial catheter (such as Rickham or Ommaya) in place
• Age ≥ 3 years
• Life expectancy ≥ 6 weeks
• Karnofsky/Lansky score ≥ 60
• Bilirubin less than or equal to 3x upper limit of normal, AST less than or equal to 5x upper limit of normal, ALT less than or equal to 5x upper limit of normal, serum creatinine less than or equal to 2x upper limit of normal for age, and Hgb greater than or equal to 7.0 g/dL
• Pulse oximetry of greater than or equal to 90% on room air
• Sexually active subjects must be willing to utilize one of the more effective birth control methods for 6 months after the T cell infusion. The male partner should use a condom
• Available autologous transduced T lymphocytes with greater than or equal to 15% expression of HER2 CAR determined by flow-cytometry and killing of HER2-positive targets greater than or equal to 20% in cytotoxicity assay
• Patients who have undergone tumor resection should have recovered from the surgery. Patients with neurological deficits should have deficits that are stable for minimum of 1 week prior to treatment.
• Subjects should have been off other investigational antineoplastic therapy for two weeks prior to CAR T cell infusion. Temozolomide will be allowed up to 48 hours pre-infusion. Dexamethasone up to a total dose of 2 mg per day will be allowed if medically indicated

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Central Nervous System Neoplasms

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Nabil M Ahmed, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

• Shoba Navai, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

• Meenakshi Hegde, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: April 1, 2016
• Primary Completion: April 27, 2022
• Study Completion (Estimated): April 1, 2037
• Last Updated: September 5, 2025

Record last verified: 2025-08

Locations

US (2)