Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Ipilimumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Haploidentical donor derived CIML NK cell infusion with subcutaneous N-803 for eligible patients with platinum-refractory and immune checkpoint blockade-refractory, advanced head and neck squamous cell carcinoma (Cohort 1)

* CIML NK cell infusion (Dose 0 or -1) infused on Day 0.
* Interleukin-15 Superagonist dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).

Cohort 2 treated with an ipilimumab lead-in prior to CIML NK cell infusion after safety is established with the NK cell and N-803 treatments alone.

* Participants in the ipilimumab subgroup (Cohort 2) will receive a single dose of lead-in ipilimumab via iv per protocol determined dose followed by lymphodepleting chemotherapy on Day -6 for a total of 5-days, prior to receiving CIML NK cell infusion.
* CIML NK cell infusion-Highest Dosed per cohort 1, infused on day 0
* Interleukin-15 Superagonist (N-803) Administration

  -- dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).
* Cohort 2 will receive the highest number of CIML NK cells that is still considered safe and ipilimumab.

Cohort 3 treated with CIML NK cell infusion after safety is established with the NK cell and N-803 treatments alone, followed by cetuximab infusions.

* - Participants in cetuximab subgroup (Cohort 3) will receive lymphodepleting chemotherapy on Day -6 for a total of 5-days, prior to receiving CIML NK cell infusion.
* CIML NK cell infusion-Highest Dosed per cohort 1, infused on day 0
* Interleukin-15 Superagonist (N-803) Administration

  -- dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).
* Cetuximab Administration

  --dosed at 500mg/m2 IV over 120 minutes for the first dose, then over 60 minutes for subsequent doses. This will be infused every 14 days for 8 doses started on day +15.
* Cohort 3 will receive the highest number of CIML NK cells that is still considered safe and ipilimumab.

-- Starting the day after (Cycle 1, Day +1) CIML NK-enriched cell infusion, at least 12 hours after CIML NK cell infusion is completed and up to 48 hours after CIML NK cell infusion, each participant will receive N-803 dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles).

N-803 dosed at 15 mcg/kg subcutaneously every 21 days for 4 total doses (a cycle being every 21-days, so 4 cycles) for cohorts 1 and 2, and 6 total doses in cohort 3. The dose should be calculated based on body weight at study entry, and recalculated only if greater than 10% change in weight.

Interleukin-15 Superagonist (N-803)

CIML NK cell Infusion

single dose of lead-in ipilimumab via iv per protocol determined dose

Starting day +15, every 14 days for 8 total doses via IV per protocol

Glenn Hanna, MD

Casey Welch

Glenn J. Hanna, MD

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
* Cetuximab

This is a three-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, participants in cohort 2 will also receive ipilimumab, and participants in cohort 3 will receive cetuximab. 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 3 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
* Cohort 3 participants will be treated at the respective dose (at or below the Maximum Tolerated Dose), as determined during Cohort plus infusions of cetuximab
* It is expected that about 25 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.

The U.S. Food and Drug Administration (FDA) has approved cetuximab for your specific disease.

CIML NK Cell in Head & Neck Cancer

A Phase 1 Trial of CTLA-4 Inhibition, With or Without Cetuximab, and in Combination With Memory-like Natural Killer (NK) Cell Immune Cell Therapy in Advanced Head & Neck Cancer

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

All patients receiving any dose of study treatment will be evaluated for safety. DLTs overall and by dose level will be reported as proportions with 90% exact binomial confidence intervals.

reported as proportions with 90% exact binomial confidence intervals for all patients and by dose level

Spots Global Cancer Trial Database for ciml nk cell infusion