CIML NK Cell in Head & Neck Cancer
CIML NK Cell in Head & Neck Cancer
This research study is evaluating the safety and efficacy of a combination drug and biologic
 therapy in patients with advanced head and neck cancer.

 This research study involves the following drugs and biologics:

 -  CIML NK donor cells

 -  IL-15 superagonist

 -  Ipilimumab
This is a two-part, non randomized, open label, single site Phase 1 study. The purpose of
 this research study is to obtain information on the safety and effectiveness of this
 combination of study drugs to treat advanced head and neck. The experimental combination
 therapy in this study involves CIML NK cells from a haploidentical donor (meaning cells from
 another person with similar immune proteins), IL-15, and participants in cohort 2 will also
 receive ipilimumab. CIML NK cells are an allogeneic cell product derived from qualified donor
 natural killer (NK) cells that have been bathed in special proteins to help to identify and
 treat certain advanced cancers.

 - Participants who fulfill eligibility criteria will be entered into the trial CTLA-4
 Inhibition in Combination with Memory-like Natural Killer (NK) Cell Immune Cell Therapy in
 Advanced Head & Neck Cancer.

 The study consists of 2 parts:

 -  Cohort 1 CIML NK cells without ipilimumab

 -  The investigators are looking the highest dose of the study intervention that can be
 administered safely without severe or unmanageable side effects in participants that
 have advanced head and neck cancer, not everyone who participates in this research study
 will receive the same dose of the study intervention. The dose given will depend on the
 number of participants who have been enrolled prior and how well the dose was tolerated

 -  Cohort 2 participants will be treated at the respective dose (at or below the Maximum
 Tolerated Dose), as determined during Cohort plus a lead-in dose of ipilimumab

 -  It is expected that about 12 people will take part in this research study.

 This research study is a Phase I clinical trial, which tests the safety of investigational
 drugs and tries to define the appropriate dose of the investigational drugs to use for
 further studies.

 "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration
 (FDA) has not approved CIML NK cells as treatment for any disease.

 The U.S. Food and Drug Administration (FDA) has not approved IL-15 as a treatment for any
 disease.

 The U.S. Food and Drug Administration (FDA) has not approved ipilimumab for your specific
 disease but it has been approved for other uses.
Inclusion Criteria:

 -  Histologically or cytologically confirmed, recurrent or metastatic squamous cell
 carcinoma of the head neck (including oral cavity, oropharynx, larynx, hypopharynx,
 paranasal sinuses)

 -  Any HPV status or smoking history is permitted. Oropharyngeal cancer patients are
 required to undergo HPV testing with p16 immunohistochemistry and/or confirmatory HPV
 PCR or ISH testing

 -  Available haploidentical donor that is willing and eligible for non-mobilized
 collection

 -  Prior exposure to a platinum-containing regimen (either in the definitive or advanced,
 recurrent/metastatic setting) and exposure to a PD-1/L1 inhibitor is required

 -  Age 18 years or older

 -  ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A).

 -  No systemic corticosteroid therapy (≤ 10 mg of prednisone or equivalent dose of
 systemic steroids for non-autoimmune indications for at least 4 weeks prior to NK cell
 infusion).

 -  Ability to understand and the willingness to sign a written informed consent document.

 -  Negative pregnancy test for women of childbearing potential only. Women of
 childbearing potential (WOCBP) must have a negative serum or urine pregnancy test
 (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours before the
 start of ipilimumab.

 -  The effects of CIML NK cells and N-803 on the developing human fetus are unknown.

 For this reason, WOCBP and men must agree to use adequate contraception (hormonal or
 barrier method of birth control; abstinence) prior to study entry and for the duration of
 study participation, and for up to 26 weeks after the last dose of all investigational
 products (up to 16 weeks after the last N-803 dose), in such a manner that the risk of
 pregnancy is minimized. Should a woman become pregnant or suspect she is pregnant while she
 or her partner is participating in this study, she should inform her treating physician
 immediately.

 -  Willing to provide blood and tissue from diagnostic biopsy and at the time of surgery

 -  Participants must have normal organ and marrow function as defined below:

 -  leukocytes ≥ 3,000/mcL

 -  absolute neutrophil count ≥ 1,500/mcL

 -  platelets ≥ 100,000/mcL

 -  total bilirubin ≤ 1.5x institutional upper limit of normal (ULN)

 -  AST(SGOT)/ALT(SGPT) ≤ 3x institutional upper limit of normal

 -  creatinine within normal institutional limits OR

 -  creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels
 above institutional normal.

 -  Oxygen saturation: ≥ 90% on room air

 -  Left ventricular ejection fraction (cardiac function) > 40%

 Exclusion Criteria:

 -  Patients with nasopharyngeal carcinoma are not eligible

 -  Participants who have had anti-tumor chemotherapy or other investigational agents
 within 4 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or
 immunotherapy within 6 weeks prior, or those who have not recovered from adverse
 events due to agents administered more than 4 weeks prior.

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to N-803 or other agents used in study.

 -  Solid organ transplant (allograft) recipients.

 -  Participants who are receiving any other investigational agents.

 -  Participants with known brain metastases should be excluded from this clinical trial
 because of their poor prognosis and because they often develop progressive neurologic
 dysfunction that would confound the evaluation of neurologic and other adverse events.

 -  Autoimmune disease: patients with a history of inflammatory bowel disease, including
 ulcerative colitis and Crohn disease, are excluded from this study, as are patients
 with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
 progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
 vasculitis [Wegener's granulomatosis]) and motor neuropathy considered of autoimmune
 origin (e.g. Guillain- Barre syndrome and myasthenia gravis). Patients with Hashimoto
 thyroiditis are eligible.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements.

 -  Pregnant women are excluded from this study because of the unknown teratogenic risk of
 CIML NK cells and N-803 and with the potential for teratogenic or abortifacient
 effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an
 unknown but potential risk for adverse events in nursing infants secondary to
 treatment of the mother with CIML NK cells and N-803, breastfeeding should be
 discontinued if the mother is treated on this study.

 -  HIV-positive participants are ineligible because of the potential for pharmacokinetic
 interactions with anti-retroviral agents used in this study. In addition, these
 participants are at increased risk of lethal infections when treated with
 marrow-suppressive therapy.

 -  Individuals with active uncontrolled hepatitis B or C are ineligible as they are at
 high-risk of lethal treatment-related hepatotoxicity in the setting of marrow
 suppression.

 -  Known non-infectious pneumonitis or any history of interstitial lung disease.

 -  Receipt of a live vaccine within 30 days of start of study treatment.

 -  Individuals receiving therapeutic anticoagulation are eligible.