| Eligibility |
Inclusion Criteria:
- Has high-risk stage II or stage III colorectal cancer and has completed
standard-of-care treatment, including complete disease resection followed by
standard-of-care adjuvant treatment and has no evidence of relapsing disease per the
CT scan but has persistent ctDNA in the bloodstream; OR has resected stage IV
colorectal cancer undergone with curative intent, has completed standard-of-care
adjuvant- and/or neo-adjuvant treatment, and has no evidence of residual disease per
the CT scan but has persistent ctDNA in the bloodstream.
- Has signed the Informed Consent Form
- Is age 18 years
- Is able to comply with the study protocol, in the investigator's judgment
- Has ECOG performance status of 0-1
- Has adequate hematologic and end-organ function defined by the following laboratory
test results obtained within 28 days prior to initiation of study treatment:
- Absolute neutrophil count (ANC) 1,500/mm3 without granulocyte colony-stimulating
factor support
- Lymphocyte count 500/mm3
- Platelet count 100,000/mm3 without transfusion
- White blood cell count 2,500/mm3
- Hemoglobin 9.0 g/dL o Patients may be transfused to meet this criterion.
- Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline
phosphatase 2.5 upper limit of normal (ULN), with the following exceptions:
- For patients with documented liver metastases: AST and ALT 5 ULN
- For patients with documented liver or bone metastases: alkaline phosphatase
5 ULN
- Serum bilirubin 1.5 ULN with the following exception:
o For patients with known Gilbert disease: serum bilirubin level 3 ULN
- Serum creatinine 1.5 ULN
- Serum albumin 2.5 g/dL
- For patients not receiving therapeutic anticoagulation: international normalized
ratio (INR) or activated partial thromboplastin time (aPTT) 1.5 ULN
- Adequate cardiac function
- Baseline EKG and echocardiogram (ECHO) within normal limits
- For women and men for childbearing potential: agreement to use a contraceptive method
with a failure rate of 1% per year or remain abstinent (refrain from heterosexual
intercourse) during the treatment period and for 6 months after the last dose of study
treatment
- A woman is considered to be of childbearing potential if she is premenarcheal,
has not reached a postmenopausal state ( 12 continuous months of amenorrhea with
no identified cause other than menopause), and has not undergone surgical
sterilization (removal of ovaries and/or uterus).
- Examples of contraceptive methods with a failure rate of 1% per year include
bilateral tubal ligation, male sterilization, barrier method, hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices,
and copper intrauterine devices.
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not acceptable methods of
contraception.
Exclusion Criteria:
- Received treatment for the studied cancer within 28 days prior to initiation of study
treatment
- Received treatment with an investigational therapy within 28 days prior to initiation
of study treatment
- Has a history of severe allergic-, anaphylactic-, or other hypersensitivity reactions
to chimeric- or humanized antibodies or fusion proteins
- Has a known hypersensitivity to biopharmaceutical agents produced in Chinese hamster
ovary cells
- Has a known allergy or hypersensitivity to any component of the expanded CB-NK cells
formulation
- Has a known allergy or hypersensitivity to any component of the cetuximab formulation
- Has active- or a history of autoimmune disease or immune deficiency, including, but
not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré
syndrome, or multiple sclerosis (also see Appendix 4), with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid
replacement hormone are eligible for the study.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:
- Rash must cover 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high potency or oral corticosteroids
within the previous 12 months
- Had prior allogeneic stem cell or solid organ transplantation
- Has history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,
bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or
evidence of active pneumonitis on screening chest computed tomography scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Had a positive HIV test at screening
- Has active hepatitis B virus (HBV) infection (chronic or acute), defined as having a
positive hepatitis B surface antigen (HBsAg) test at screening
• Patients with a past or resolved HBV infection, defined as having a negative HBsAg
test and a positive total hepatitis B core antibody (HBcAb) test and negative HBV DNA
test at screening, are eligible for the study.
- Has active hepatitis C virus (HCV) infection, defined as having a positive HCV
antibody test followed by a positive HCV RNA test at screening
• The HCV RNA test will be performed only for patients who have a positive HCV
antibody test.
- Has active tuberculosis
- Had a severe infection within 4 weeks prior to initiation of study treatment,
including, but not limited to, hospitalization for complications of infection,
bacteremia, or severe pneumonia
- Had treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks
prior to initiation of study treatment
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract
infection or chronic obstructive pulmonary disease exacerbation) are eligible for the
study.
- Has significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction, unstable arrhythmia, unstable
angina, or cerebrovascular accident within 3 months prior to initiation of study
treatment
- Had a major surgical procedure, other than for diagnosis, within 4 weeks prior to
initiation of study treatment, or anticipates needing a major surgical procedure
during the course of the study
- Received treatment with a live, attenuated vaccine within 4 weeks prior to initiation
of study treatment, or anticipates needing such a vaccine during the course of the
study, or up to 5 months following the anticipated dose of expanded CB-NK cells.
- Had a malignancy other than the disease under study within 5 years prior to receipt of
expanded CB-NK cell therapy.
• Allowed are (1) those with a negligible risk of metastasis or death and with
expected curative outcome (such as adequately treated carcinoma in situ of the cervix,
basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically
with curative intent); or (2) those undergoing active surveillance per
standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0)
- Has any other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding that contraindicates the use of an investigational drug,
may affect the interpretation of the results, or may render the patient at high risk
from treatment complications
- Had treatment with any immune checkpoint blockade therapy, including antiCTLA-4,
antiPD-1, or antiPD-L1 therapeutic antibodies, within 4 weeks or five half-lives of
the drug prior to initiation of this study
- Received treatment with systemic immunostimulatory agents (including, but not limited
to, interferon and interleukin 2) within 4 weeks or five half-lives of the drug
(whichever is longer) prior to initiation of study treatment
- Received treatment with systemic immunosuppressive medication (including, but not
limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and antiTNF- agents) within 2 weeks prior to initiation of study
treatment, or anticipates needing systemic immunosuppressive medication during the
course of the study, with the following exceptions:
- Patients who received low-dose immunosuppressant medication are eligible for the
study.
- Patients with active immunological disease requiring more than 10 mg of steroids
daily are eligible for the study.
- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids
for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids
for orthostatic hypotension or adrenal insufficiency are eligible for the study.
- Is pregnant or breastfeeding, or intends to become pregnant during the study • Women
of childbearing potential must have a negative serum pregnancy test result within 14
days prior to initiation of study treatment.
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