Study of B7-H3-Specific CAR T Cell Locoregional Immunotherapy for Diffuse Intrinsic Pontine Glioma/Diffuse Midline Glioma and Recurrent or Refractory Pediatric Central Nervous System Tumors

  • STATUS
    Recruiting
  • End date
    May 22, 2041
  • participants needed
    70
  • sponsor
    Seattle Children's Hospital
Updated on 22 March 2021
tumor resection
MRI
dexamethasone
tumor cells
apheresis
cns disease
cancer chemotherapy
supratentorial tumors
dipg
cns tumor
tumour resection
cns neoplasm
diffuse intrinsic pontine glioma
central nervous system tumor
mg++

Summary

This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced to express a B7H3-specific chimeric antigen receptor (CAR) and EGFRt. CAR T cells are delivered via an indwelling catheter into the tumor resection cavity or ventricular system in children and young adults with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), and recurrent or refractory CNS tumors.

A child or young adult meeting all eligibility criteria, including having a CNS catheter placed into the tumor resection cavity or into their ventricular system, and meeting none of the exclusion criteria, will have their T cells collected. The T cells will then be bioengineered into a second-generation CAR T cell that targets B7H3-expressing tumor cells. Patients will be assigned to one of 3 treatment arms based on location or type of their tumor. Patients with supratentorial tumors will be assigned to Arm A, and will receive their treatment into the tumor cavity. Patients with either infratentorial or metastatic/leptomeningeal tumors will be assigned to Arm B, and will have their treatment delivered into the ventricular system. The first 3 patients enrolled onto the study must be at least 15 years of age and assigned to Arm A or Arm B. Patients with DIPG will be assigned to Arm C and have their treatment delivered into the ventricular system. The patient's newly engineered T cells will be administered via the indwelling catheter for two courses. In the first course patients in Arms A and B will receive a weekly dose of CAR T cells for three weeks, followed by a week off, an examination period, and then another course of weekly doses for three weeks. Patients in Arm C will receive a dose of CAR T cells every other week for 3 weeks, followed by a week off, an examination period, and then dosing every other week for 3 weeks. Following the two courses, patients in all Arms will undergo a series of studies including MRI to evaluate the effect of the CAR T cells and may have the opportunity to continue receiving up to a total of six courses of CAR T cells if the patient has not had adverse effects and if more of their T cells are available.

The hypothesis is that an adequate amount of B7H3-specific CAR T cells can be manufactured to complete two courses of treatment with 3 or 2 doses given on a weekly schedule followed by one week off in each course. The other hypothesis is that B7H3-specific CAR T cells can safely be administered through an indwelling CNS catheter or delivered directly into the brain via indwelling catheter to allow the T cells to directly interact with the tumor cells for each patient enrolled on the study. Secondary aims of the study will include evaluating CAR T cell distribution with the cerebrospinal fluid (CSF), the extent to which CAR T cells egress or traffic into the peripheral circulation or blood stream, and, if tissues samples from multiple timepoints are available, also evaluate disease response to B7-H3 CAR T cell locoregional therapy.

Details
Condition Ependymoma, Medulloblastoma, Neuroectodermal Tumor, Glioma, Central Nervous System Neoplasms, Primitive neuroectodermal tumor, Germ cell tumor, Diffuse Intrinsic Pontine Glioma, Atypical Teratoid/Rhabdoid Tumor, DIPG, Atypical Teratoid Rhabdoid Tumor, Choroid Plexus Carcinoma, Neurectoderma, Diffuse Midline Glioma, Gliomas, Germ Cell Tumors, Pineoblastoma, Childhood, Pineoblastoma, Childhood, Pineoblastoma, Childhood, Pineoblastoma, Childhood, cns tumors, cns tumor, cns neoplasm, central nervous system tumors, central nervous system tumor, primitive neuroectodermal tumour, pnet, glial tumor, Pineoblastoma, Childhood, Pineoblastoma, Childhood, Pineoblastoma, Childhood
Treatment SCRI-CARB7H3(s); B7H3-specific chimeric antigen receptor (CAR) T cel
Clinical Study IdentifierNCT04185038
SponsorSeattle Children's Hospital
Last Modified on22 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 1 and 26 years
Diagnosis of refractory or recurrent CNS disease for which there is no standard therapy, or diagnosis of DIPG or DMG at any time point following completion of standard therapy
Able to tolerate apheresis, or has apheresis product available for use in manufacturing
CNS reservoir catheter, such as an Ommaya or Rickham catheter
Life expectancy 8 weeks
Lansky or Karnofsky score 60
If patient does not have previously obtained apheresis product, patient must have discontinued, and recovered from acute toxic effects of, all prior chemotherapy, immunotherapy, and radiotherapy and discontinue the following prior to enrollment
Adequate organ function
7 days post last chemotherapy/biologic therapy administration
Adequate laboratory values
3 half lives or 30 days, whichever is shorter post last dose of anti-tumor antibody therapy
Patients of childbearing/fathering potential must agree to use highly effective contraception
Must be at least 30 days from most recent cellular infusion
All systemically administered corticosteroid treatment therapy must be stable or decreasing within 1 week prior to enrollment with maximum dexamethasone dose of 2.5 mg/m2/day. Corticosteroid physiologic replacement therapy is allowed

Exclusion Criteria

Presence of Grade 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention
Presence of primary immunodeficiency/bone marrow failure syndrome
Presence of clinical and/or radiographic evidence of impending herniation
Presence of >Grade 3 dysphagia
Presence of active malignancy other than the primary CNS tumor under study
Presence of active severe infection
Receiving any anti-cancer agents or chemotherapy
Pregnant or breastfeeding
Subject and/or authorized legal representative unwilling or unable to provide consent/assent for participation in the 15 year follow up period
Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
Clear my responses

How to participate?

Step 1 Connect with a site
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
Name

Primary Contact

site
Name

Phone Email

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

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