Brief Title
HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors
Official Title
Phase 1 Study of HER2-Specific CAR T Cell Locoregional Immunotherapy for HER2 Positive Recurrent/Refractory Pediatric Central Nervous System Tumors
Brief 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 HER2-specific chimeric
antigen receptor (CAR) and EGFRt, delivered by an indwelling catheter in the tumor resection
cavity or ventricular system in children and young adults with recurrent or refractory
HER2-positive CNS tumors. A child or young adult with a refractory or recurrent CNS tumor
will have their tumor tested for HER2 expression by immunohistochemistry (IHC) at their home
institution or at Seattle Children's Hospital. If the tumor is HER2 positive and the patient
meets all other eligibility criteria, including having a CNS catheter placed into the tumor
resection cavity or into their ventricular system, and meets none of the exclusion criteria,
then they can be apheresed, meaning T cells will be collected. The T cells will then be
bioengineered into a second-generation CAR T cell that targets HER2-expressing tumor cells.
The patient's newly engineered T cells will then be administered via the indwelling CNS
catheter for two courses. In the first course they 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. Following the two courses, patient's 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 HER2-specific CAR T cells can be manufactured to
complete two courses of treatment with three doses given on a weekly schedule followed by one
week off in each course. The other hypothesis is that HER-specific CAR T cells safely can be
administered through an indwelling CNS catheter to allow the T cells to directly interact
with the tumor cells for each patient enrolled on the study safely can be delivered directly
into the brain via indwelling catheter. Secondary aims of the study will include to evaluate
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 time points are available, also evaluate the degree of HER2 expression at
diagnosis versus at recurrence.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Establish the safety, defined by the adverse events, of HER2-specific CAR T cell infusions delivered by a central nervous system (CNS) catheter into the tumor resection cavity or ventricular system
Secondary Outcome
Assess the distribution of CNS-delivered HER2-specific CAR T cells within the cerebrospinal fluid (CSF) and peripheral blood
Condition
Central Nervous System Tumor, Pediatric
Intervention
HER2-specific chimeric antigen receptor (CAR) T cell
Study Arms / Comparison Groups
ARM A (Tumor Cavity Infusion)
Description: patients with supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity Intervention: HER2-specific chimeric antigen receptor (CAR) T cell
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
48
Start Date
July 26, 2018
Completion Date
July 26, 2039
Primary Completion Date
July 26, 2024
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 1 and ≤ 26 years
2. Histologically diagnosed HER2-positive Central Nervous System (CNS) tumor
3. Evidence of refractory or recurrent CNS disease for which there is no standard therapy
4. Able to tolerate apheresis, or has apheresis product available for use in
manufacturing
5. CNS reservoir catheter, such as an Ommaya or Rickham catheter
6. Life expectancy ≥ 8 weeks
7. Lansky or Karnofsky score ≥ 60
8. If patient does not have previously obtained apheresis product, patient must have
recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and
radiotherapy and discontinue the following prior to enrollment:
1. ≥ 7 days post last chemotherapy/biologic administration
2. 3 half-lives or 30 days, whichever is shorter post last dose of anti-tumor
antibody therapy
3. Must be at least 30 days from most recent cell infusion
4. 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.
9. Adequate organ function
10. Adequate laboratory values
11. Patients of childbearing/fathering potential must agree to use highly effective
contraception
Exclusion Criteria:
1. Diagnosis of classic diffuse intrinsic pontine glioma (DIPG)
2. Presence of Grade ≥ 3 cardiac dysfunction or symptomatic arrhythmia requiring
intervention
3. Presence of primary immunodeficiency/bone marrow failure syndrome
4. Presence of clinical and/or radiographic evidence of impending herniation
5. Presence of active malignancy other than the primary CNS tumor under study
6. Presence of active severe infection
7. Receiving any anti-cancer agents or chemotherapy
8. Pregnant or breastfeeding
9. Subject and/or authorized legal representative unwilling or unable to provide
consent/assent for participation in the 15-year follow up period
10. Presence of any condition that, in the opinion of the investigator, would prohibit the
patient from undergoing treatment under this protocol
Gender
All
Ages
1 Year - 26 Years
Accepts Healthy Volunteers
No
Contacts
Nicholas Vitanza, MD, 206-987-2106, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03500991
Organization ID
BrainChild-01
Responsible Party
Principal Investigator
Study Sponsor
Seattle Children's Hospital
Study Sponsor
Nicholas Vitanza, MD, Study Chair, Seattle Children's Hospital
Verification Date
March 2021