HER2-specific CAR T Cell Locoregional Immunotherapy for HER2-positive Recurrent/Refractory Pediatric CNS Tumors
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Brain Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 1 - 26 |
| Updated: | 12/19/2018 |
| Start Date: | July 26, 2018 |
| End Date: | July 26, 2036 |
| Contact: | Nicholas Vitanza, MD |
| Email: | CBDCIntake@seattlechildrens.org |
| Phone: | 206-987-2106 |
Phase 1 Study of HER2-Specific CAR T Cell Locoregional Immunotherapy for HER2 Positive Recurrent/Refractory Pediatric Central Nervous System Tumors
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.
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.
Inclusion Criteria:
- First 3 enrolled subjects: age ≥ 15 and ≤ 26 years Subsequent subjects: age ≥ 1 and ≤
26 years
- Histologically diagnosed HER2-positive Central Nervous System (CNS) tumor
- Evidence of refractory or recurrent CNS disease that has failed first-line therapy
- Willing and able to provide tumor specimens
- Able to tolerate apheresis
- CNS reservoir catheter, such as an Ommaya or Rickham catheter
- Life expectancy ≥ 8 weeks
- Lansky or Karnofsky score ≥ 60
- Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and
radiotherapy
- ≥ 7 days post last chemotherapy administration
- 3 half-lives or 30 days, whichever is shorter post last dose of anti-tumor antibody
therapy
- No prior virotherapy. Prior genetically modified cell therapy is allowed if not
detectable at enrollment.
- Stable or decreasing dosing of steroid treatment for symptomatic relief from CNS
disease, with maximum dexamethasone dose of 2.5 mg/m2/day
- Adequate organ function
- Adequate laboratory values
- Patients of childbearing/fathering potential must agree to use highly effective
contraception
Exclusion Criteria:
- Diagnosis of classic diffuse intrinsic pontine glioma (DIPG)
- 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 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
We found this trial at
1
site
4800 Sand Point Way NE
Seattle, Washington 98105
Seattle, Washington 98105
(206) 987-2000
Principal Investigator: Nicholas Vitanza, MD
Seattle Children's Hospital Seattle Children’s Hospital specializes in meeting the unique physical, emotional and developmental...
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