Inclusion Criteria:
- - SCREENING: Participant has treated brain and/or leptomeningeal metastases that has
not recurred OR.
- - Such participants are eligible to enroll in the study and undergo
leukapheresis, but they cannot start treatment with HER2-CAR T cells until
there is evidence of tumor progression/recurrence.
- - SCREENING: Participant has recurrent brain metastases after radiation therapy OR.
- - SCREENING: Participant has recurrent leptomeningeal metastases after intrathecal
chemotherapy OR.
- - SCREENING: Participant has untreated brain or leptomeningeal metastases and refuses
to undergo radiation and/or intrathecal chemotherapy.
- - Note: Participants with leptomeningeal metastasis (diagnosed by positive CSF
cytology or characteristic findings on brain or spine magnetic resonance
imaging [MRI]) may have concomitant brain metastases, but having both is not
required.
- - SCREENING: Participant must have a Karnofsky performance status (KPS) >= 70.
- - SCREENING: Participant must have a life expectancy of >= 8 weeks.
- - SCREENING: The effects of HER2-CAR T cells on a developing fetus are unknown.
For
this reason, women of child-bearing potential must have negative serum pregnancy
test and agree to use a reliable form of birth control prior to study entry and for
at least two months following duration of study participation. Male research
participants must agree to use a reliable form of birth control and not donate sperm
during the study and for at least six months afterwards.
- - SCREENING: Participant has a histologically confirmed cancer which is HER2+, defined
as 3+ by immunohistochemistry (IHC) or gene amplification by fluorescence in situ
hybridization (FISH)
- SCREENING: Participant must have the ability to understand and the willingness to
sign a written informed consent.
- - ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: At least 2 weeks must have elapsed since
the participant received his/her last dose of prior targeted agents, chemotherapy or
radiation; at the PI's discretion, exception can be made for investigational agents
that are delivered locally into the CSF.
- - ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: Research participant must not require
more than 6 mg/day of dexamethasone (or the equivalent dose of another
corticosteroid) on the day of leukapheresis.
- - ELIGIBILITY TO PROCEED WITH LEUKAPHERESIS: Participant must be willing to undergo
placement of a catheter for central venous access if s/he does not have adequate
peripheral venous access for collection of T cells.
- - ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Creatinine < 1.6 mg/dL.
- - ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: White blood cell (WBC) >
2,000/uL (or absolute neutrophil count [ANC] > 1,000)
- ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Platelets >= 100,000/uL.
- - ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: International normalized
ratio (INR) must be < 1.3.
- - ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Bilirubin < 1.5 mg/dL.
- - ELIGIBILITY TO PROCEED WITH RICKHAM RESERVOIR PLACEMENT: Alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) < 2.5 X upper limits of normal.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Participant must be taking =< 6 mg/ day of dexamethasone (or the
equivalent dose of another corticosteroid) during CAR T cell therapy.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Participants agrees to stop treatment with chemotherapy or
endocrine therapy during the first 3 cycles of the HER2-CAR T cell study.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Participant does not have evidence of active infection and does
not have a fever exceeding 38.5 degrees C; there is an absence of positive blood
culture for bacteria, fungus, or virus within 48-hours prior to HER2-CAR T cell
infusion and/or there aren't any indications of meningitis.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: WBC > 2,000/uL (or ANC > 1,000)
- ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Platelets > 100,000/uL.
However, if platelet level is between
75,000-99,000/uL then HER2-CAR T-cell administration may proceed after platelet
transfusion is given, and the post transfusion platelet count is >= 100,000/uL.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Serum creatinine < 1.8 mg/dL.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Serum total bilirubin or transaminases does not exceed 2 X upper
limits of normal.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Research participant does not require supplemental oxygen to keep
saturation greater than 95% and/or does not have presence of any radiographic
abnormalities on chest x-ray that are positive.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Research participant does NOT have any known history of congestive
heart failure (CHF) or cardiac symptoms consistent with New York Heart Association
(NYHA) classification III-IV within 6 months prior to day 1 of protocol treatment,
cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic
medications or with clinical history suggestive of the above must have an
electrocardiogram (EKG) and echocardiogram (ECHO) performed within 42 days prior to
registration and as clinically indicated while on treatment.
- - If the research participant has new symptoms of congestive heart failure (CHF),
cardiomyopathy, myocarditis, MI, or exposure to cardiotoxic medications, they
already had a cardiac consultation, creatinine phosphokinase (CPK), and
troponin testing at pre study deeming them fit for study participation.
- - ELIGIBILITY FOR ENROLLMENT AND TO PROCEED WITH INTRAVENTRICULAR ADMINISTRATION OF
HER2-CAR T CELLS: Participant has a released cryopreserved HER2-CAR T cell product.
- - ADDITIONAL ELIGIBILITY TO START CYCLE 1: Participant must have at least 1 metastatic
brain lesion (measurable disease per RANO-Brain Metastases [BM] is not
required-i.e., participant does not need to have at least 1 metastatic lesion >= 1
cm in longest dimension) that is new or increasing in size, or CSF cytology and/or
radiographic findings consistent with leptomeningeal metastases.
- - ADDITIONAL ELIGIBILITY TO START CYCLE 1: Participants whose brain metastases have
been treated with whole brain radiation (WBRT) or stereotactic radiosurgery (SRS):
previously radiated metastases must have >= 20% increase in longest diameter that is
also >= 5 mm absolute increase from prior brain MRI or histopathologically proven
recurrent tumor.
Otherwise, new or not previously radiated lesions must be present.
- - Note: Participants who have undergone local therapy (surgical resection or
biopsy, or SRS), must have recovered from all acute side effects before
starting treatment with HER2-CAR T cells.
- - ADDITIONAL ELIGIBILITY TO START CYCLE 1: If a participant with brain metastases does
not meet the above criteria, but there is still concern by the study team that
changes in an enhancing brain lesion seen on brain MRI could be due to tumor
progression, then the participant can undergo resection or biopsy of the lesion(s)
to distinguish between tumor progression versus radiation necrosis.
If there is
histopathological evidence of tumor progression, then the participant can proceed
with study treatment.
- - ADDITIONAL ELIGIBILITY TO START CYCLE 1: Research participant does not have
uncontrolled seizure following surgery prior to starting the first CAR T cell dose.
- - ADDITIONAL ELIGIBILITY TO START CYCLE 1: Participants must have recovered from
toxicity (=< grade 1) of prior therapy (excluding alopecia and peripheral
neuropathy)
- ADDITIONAL ELIGIBILITY TO START CYCLE 1: Wash-out requirements (standard or
investigational).
The required waiting period between the last dose of the most
recent chemotherapy agent(s) and first dose of HER2-CAR T cells is:
- - Four weeks for a cytotoxic chemotherapy, except for capecitabine, which will
only require a 1 week waiting period from the last dose (on a dosing schedule
of bid x 14 days, then off x 7 days);
- At least 6 weeks must have passed since the completion of a
nitrosourea-containing chemotherapy regimen;
- At least four half-lives for a targeted agent.
Exclusion Criteria:
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Research participant requires supplemental
oxygen to keep saturation greater than 95% and the situation is not expected to
resolve within 2 weeks.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Research participants with a known history
of congestive heart failure (CHF) or cardiac symptoms consistent with NYHA
classification III-IV within 6 months prior to day 1 of protocol treatment,
cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic
medications or with clinical history suggestive of the above must have an EKG and
echocardiogram (ECHO) performed within 42 days prior to registration and as
clinically indicated while on treatment.
- - Research participants with new symptoms of CHF, cardiomyopathy, myocarditis,
MI, or exposure to cardiotoxic medications must have a cardiac consultation,
creatinine phosphokinase (CPK), and troponin testing at pre study and as
clinically indicated.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Research participant requires dialysis.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Research participant has uncontrolled
seizure activity and/or clinically evident progressive encephalopathy.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Failure of research participant to
understand the basic elements of the protocol and/or the risks/benefits of
participating in this phase 1 study.
A legal guardian may substitute for the
research participant.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is unwilling to stop treatment
with chemotherapy or endocrine therapy during the first 3 cycles of the HER2-CAR T
cell study.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has a coagulopathy or bleeding
disorder or cannot safely discontinue anticoagulation prior to placement of a
Rickham reservoir.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has a chronic or active viral
infection of the CNS.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has any uncontrolled illness,
including ongoing or active infection; participant has known active hepatitis B or C
infection; participants with any signs or symptoms of active infection, positive
blood cultures or radiological evidence of infections.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is human immunodeficiency virus
(HIV) seropositive based on testing performed within 4 weeks of screening.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has an autoimmune disease.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant has another active malignancy.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participants with lung metastases (exception
may be allowed per principal investigator [PI] discretion for participants that are
not symptomatic from their lung metastases)
- EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is unable to undergo a brain MRI.
- - EXCLUSION CRITERIA FOR STUDY SCREENING: Participant is breast feeding.
Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with HER2-CAR T cells, breastfeeding should be discontinued
if the mother wants to participate in this study. - EXCLUSION CRITERIA FOR STUDY SCREENING: Patient has a serious medical or psychiatric
illness that could, in the investigator's opinion, potentially interfere with the
safety monitoring requirements and completion of treatment according to this
protocol
