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Trial record 30 of 258 for:    "methodist hospital" | Recruiting, Not yet recruiting, Available Studies | Houston

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

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ClinicalTrials.gov Identifier: NCT02442297
Recruitment Status : Recruiting
First Posted : May 13, 2015
Last Update Posted : February 6, 2019
Sponsor:
Collaborators:
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Information provided by (Responsible Party):
Nabil Ahmed, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Brain Tumor, Recurrent Brain Tumor, Refractory Biological: HER2-specific T cells Phase 1

  Show Detailed Description

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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 2020
Estimated Study Completion Date : January 2031

Arm Intervention/treatment
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.
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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Median amount of HER2-specific T cells in the Patients' Blood [ Time Frame: 15 years ]
    To evaluate the persistence, expansion and function of HER2-specific T cells

  2. Number of Patients with a tumor response [ Time Frame: 6 weeks ]
    To evaluate the effects of gene modified T cells on measurable disease.



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • Subjects having a tumor resection if medically feasible
  • 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
  • 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 defines as: Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100% 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 normal, AST less than or equal to 5x normal, ALT less than or equal to 5x, serum creatinine less than or equal to 2x upper limit of normal for age, and Hgb greater than or equal to 7.0
  • 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
  • Subjects should have been off other investigational antineoplastic therapy for two weeks prior to entry in this study. Temozolomide will be allowed up to 48 hours preinfusion. 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)

Information from the National Library of Medicine

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


Contacts
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Contact: Nabil M Ahmed, MD 832-824-4611 nmahmed@txch.org
Contact: Josalind Randall 832-824-6835 jxrandal@txch.org

Locations
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United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Nabil M Ahmed, MD    832-824-4611    nmahmed@txch.org   
Contact: Josalind Randall    832-824-6835    jxrandal@txch.org   
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Shoba Navai, MD    832-824-7482    sanavai@txch.org   
Contact: Josalind Randall    832-824-6835    jxrandal@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Investigators
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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

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Responsible Party: Nabil Ahmed, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02442297     History of Changes
Other Study ID Numbers: H-31973-iCAR
First Posted: May 13, 2015    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019

Keywords provided by Nabil Ahmed, Baylor College of Medicine:
CNS Tumors
T cells Expressing HER2-specific Chimeric Antigen Receptors
HER2-specific T cells
intracranial injection

Additional relevant MeSH terms:
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Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases