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

  • STATUS
    Recruiting
  • End date
    Jan 13, 2036
  • participants needed
    28
  • sponsor
    Baylor College of Medicine
Updated on 13 May 2022
cancer
growth factor
dexamethasone
tumor cells
HER2
EGFR
temozolomide
malignant brain tumor
nervous
tumour resection
cns neoplasm

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.

Description

First, to find out if HER2 is expressed in the patient's brain cancer, the investigators will need to obtain the tissue block or tissue specimen that was used to make the original diagnosis. If there is enough material, investigators may also look for other proteins that may be targets for this sort of immune therapy in the future. Up to 90mls (18 tsp) of blood will be drawn on two occasions for a total of 180mls (36tsp). The total amount of blood drawn will not be more than 3 ml (less than 1 teaspoon) per 2.2 lbs of body weight.

To make HER2 CAR T cells the investigators will introduce the HER2 CAR gene into patient's T cells. To get the HER2 antibody to attach to the surface of the T cells, investigators will insert the antibody gene into the T cells. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps the investigators find the T cells in patient's blood after they inject them. Most of the cells generated will be frozen and stored to give back to the patient.

This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dosing schedule (1 of 3 different levels) of T cells. Once that dose schedule proves safe, the next group of patients will be started at a higher schedule. This process will continue until all 3 dose schedules are studied. If the side effects are too severe, the dose will be lowered or the T-cell infusions will be stopped.

The patient will be given three injections of cells two weeks apart into a special catheter that a neurosurgeon will implant into the tumor or the cavity left in the brain after surgical removal or into the fluid-filled space in your brain. The first injection of cells you receive will be the lowest dose. The subsequent injections, depending on the patient's assigned dosing schedule, may be higher than the first. Before the patient receives each injection, they may be given a dose of Tylenol. Each injection will take between 1 and 10 minutes. The patient will be admitted for overnight observation after each T-cell injection. Injections of T cells will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.

If the patient has stable disease (the tumor did not grow), a reduction in the size of the tumor on imaging studies, or unconfirmed progressive disease, but health status is stable after the start of T-cell injections (at least 6 weeks after), they can receive additional doses of the T cells at 2 to 4 week intervals if they wish. Additional doses of T cells will be given at the highest cell dose the patient receives during the initial three cell infusions. Therefore, the dose the patient receives for additional doses may be higher than the initial dose they received.

Before being treated, the patient will receive a series of standard medical tests: physical exam, blood tests to measure blood cells, kidney and liver function,' pregnancy test if the patient is a female who could potentially become pregnant or might be pregnant, measurements of patient's tumor by routine imaging studies.

The patient will receive standard medical tests when they are getting the infusions and after: physical exams, blood tests to measure blood cells, kidney and liver function, measurements of patient's tumor by routine imaging studies 6 weeks after the infusion.

To learn more about the way the HER2-CAR T cells are working and how long they last in the body, an extra amount of blood, based on patient's weight, up to a maximum of 60 mL (12 teaspoons) of blood will be taken on the day of the T-cell infusion (before and 1 to 4 hours after the T-cell infusion), 3-4 days after the infusion (this one is optional), 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months for 1 year, every 6 months for 4 years, then yearly for a total of 15 years. This volume is considered safe, but may be decreased if the patient is anemic. This sample will be kept in a coded manner so that only the study staff may identify the patient.

During the time points listed above, if the T cells are found in patient's blood at a certain amount, an extra 5ml of blood may need to be collected for additional testing.

To see if there are any long-term side effects of gene transfer, the investigators will follow the patient up to 15 years.

If the patient receives additional T-cell infusions after the first one, s/he will have the same tests and blood draws as described above.

If the patient has a tumor biopsy or lumbar puncture to obtain CSF performed any time while s/he are on the study, a sample of this will be requested for research purposes.

If the patient develops a second abnormal growth, significant blood or nervous system disorder during the trial, a biopsy sample of the tissue will be tested for research purposes (if a sample can be obtained).

Details
Condition Brain Tumor, Recurrent, Brain Tumor, Refractory
Treatment HER2-specific T cells
Clinical Study IdentifierNCT02442297
SponsorBaylor College of Medicine
Last Modified on13 May 2022

Eligibility

Yes No Not Sure

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

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)
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note