Clinical Trials /

CIML NK Cell in Head & Neck Cancer

NCT04290546

Description:

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

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CIML NK Cell in Head & Neck Cancer
  • Official Title: A Phase 1 Trial of CTLA-4 Inhibition in Combination With Memory-like Natural Killer (NK) Cell Immune Cell Therapy in Advanced Head & Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-505
  • NCT ID: NCT04290546

Conditions

  • Squamous Cell Carcinoma of the Head and Neck
  • Recurrent Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
Interleukin-15 Superagonist (N-803)Cohort 2 with Ipilimumab Lead In
CIML NK cell Infusioncytokine induced memory-like natural killerCohort 2 with Ipilimumab Lead In
IpilimumabCTLA-4 inhibitorCohort 2 with Ipilimumab Lead In

Purpose

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

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort I without Ipilimumab Lead inExperimentalHaploidentical 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).
  • Interleukin-15 Superagonist (N-803)
  • CIML NK cell Infusion
Cohort 2 with Ipilimumab Lead InExperimentalCohort 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.
  • Interleukin-15 Superagonist (N-803)
  • CIML NK cell Infusion
  • Ipilimumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Dose Limiting Toxicity
Time Frame:first dose of study treatment up to 100 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:objective response rate (ORR)
Time Frame:12 weeks
Safety Issue:
Description:reported as proportions with 90% exact binomial confidence intervals for all patients and by dose level
Measure:complete response (CR) rate
Time Frame:12 weeks
Safety Issue:
Description:reported as proportions with 90% exact binomial confidence intervals for all patients and by dose level
Measure:disease-free survival (DFS)
Time Frame:1 year
Safety Issue:
Description:Kaplan and Meier
Measure:overall survival (OS) at 1-year following infusion
Time Frame:1 year
Safety Issue:
Description:Kaplan and Meier

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Squamous Cell Carcinoma of the Head and Neck
  • Recurrent Head and Neck Squamous Cell Carcinoma

Last Updated

February 28, 2020