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ACTIVE NOT RECRUITING

NCT02442297

PHASE1

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

Sponsor: Baylor College of Medicine

View on ClinicalTrials.gov

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.

Official title: Phase I Study of Intracranial Injection of T Cells Expressing HER2-specific Chimeric Antigen Receptors (CAR) in Subjects With HER2-Positive Tumors of the Central Nervous System (iCAR)

Key Details

Gender

All

Age Range

3 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2016-04-01

Completion Date

2037-04

Last Updated

2025-09-05

Healthy Volunteers

Conditions

Brain Tumor, Recurrent Brain Tumor, Refractory

Interventions

BIOLOGICAL

HER2-specific T cells

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.

Inclusion criteria at the time of procurement. * 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 Exclusion Criteria at the time of procurement: * Diagnosis of DIPG * Bulky tumors causing midline shift and/or symptoms/signs due to impending herniation * Known HIV positivity Treatment Inclusion criteria: * 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 * Informed consent explained to, understood by and signed by research subjects/guardian. Subject/guardian given copy of informed consent. Treatment Exclusion Criteria: * Severe intercurrent infection * Known HIV positivity * Pregnant or lactating * History of hypersensitivity reactions to murine protein-containing products. * Diagnosis of DIPG * Steroid dose of dexamethasone greater than 2 mg per day (or equivalent)

Locations (2)

Houston Methodist Hospital

Houston, Texas, United States

Texas Children's Hospital