T Cells Expressing HER2-specific Chimeric Antigen Receptors(CAR) for Patients With HER2-Positive CNS Tumors (iCAR)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02442297 |
Recruitment Status :
Recruiting
First Posted : May 13, 2015
Last Update Posted : May 6, 2022
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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.
Condition or disease | Intervention/treatment | Phase |
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Brain Tumor, Recurrent Brain Tumor, Refractory | Biological: HER2-specific T cells | Phase 1 |

Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 28 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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) |
Study Start Date : | February 2016 |
Estimated Primary Completion Date : | February 2026 |
Estimated Study Completion Date : | January 2036 |
Arm | Intervention/treatment |
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Experimental: HER2-specific T cells - High Risk
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.
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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. Other Name: Dosing Schedules 1, 2, and 3 |
Experimental: HER2-specific T cells - Standard Risk
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.
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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. Other Name: Dosing Schedules 1, 2, and 3 |
- Number of patients with dose limiting toxicity after administration of autologous T cells expressing transgenic chimeric antigen receptors (CAR) targeting the HER2 molecule [ Time Frame: 6 weeks ]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.
- Number of Patients with a tumor response [ Time Frame: 6 weeks ]To evaluate the effects of gene modified T cells on measurable disease.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 3 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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:
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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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02442297
Contact: Nabil M Ahmed, MD | 832-824-4611 | nmahmed@txch.org | |
Contact: David Allen | 832-441-6279 | dlallen@texaschildrens.org |
United States, Texas | |
Houston Methodist Hospital | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Nabil M Ahmed, MD 832-824-4611 nmahmed@txch.org | |
Contact: David Allen 832-441-6279 dlallen@texaschildrens.org | |
Texas Children's Hospital | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Shoba Navai, MD 832-824-7482 sanavai@txch.org | |
Contact: David Allen 832-441-6279 dlallen@texaschildrens.org |
Principal Investigator: | 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 |
Responsible Party: | Nabil Ahmed, Assistant Professor, Baylor College of Medicine |
ClinicalTrials.gov Identifier: | NCT02442297 |
Other Study ID Numbers: |
H-31973-iCAR |
First Posted: | May 13, 2015 Key Record Dates |
Last Update Posted: | May 6, 2022 |
Last Verified: | May 2022 |
CNS Tumors T cells Expressing HER2-specific Chimeric Antigen Receptors HER2-specific T cells intracranial injection |
Neoplasms Brain Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms |
Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases |