Phase I Study on Tolerability, Safety and Efficacy of Combination Therapy of iPS-NKT Cell and Autologous DC/Gal in patients with Recurrent or Advanced Head and Neck Cancer (Combination therapy of iPS-NKT cell and DC/Gal)
Combination therapy of iPS-NKT cell and DC/Gal (Combination therapy of iPS-NKT cell and DC/Gal)
Ohtori Seiji
Iinuma Tomohisa
Chiba University Hospital
1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, JAPAN
+81-43-222-7171
iinuma-t@chiba-u.jp
Mori Shigemasa
Chiba university Hospital
1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, JAPAN
+81-43-222-7171
byoin-kshien@chiba-u.jp
6
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
Patients who meet all of the following criteria are eligible
1) Patients with recurrent or advanced head and neck cancer that is refractory or intolerant to standard therapy and who have evaluable disease that can be treated with intra-arterial injection of iPS-NKT cells.
2) Patients who are expected to have at least 1 month between prior therapy and the start of study treatment. The type of previous treatment is not required.
3) Patients must be between 20 and 80 years of age at the time of consent.
4) Patients with an ECOG performance status of 2 or less.
5) Patients with the following laboratory data.
Hemoglobin >= 10 g/dL
White blood cell count >= 3,000/uL, platelet count >= 75,000/uL
Serum creatine<= 1.5 mg/dL
Total bilirubin <=1.5 mg/dL, AST (GOT), ALT (GPT) <=2.5 times the upper limit of the institutional standard
SpO2 (room air) >= 93 %
6) Patients who are expected to have a prognosis of at least 3 months.
7) Patients with written consent.
Patients who meet any of the following conditions are not eligible
1) Patients who are HBs, HCV, HIV or HTLV-1 antibody-positive or HTLV-1 antibody-negative but have HBV-DNA detected by HBV-DNA quantitative testing.
2) Patients who have been taking or injecting corticosteroids (methylprednisolone 10 mg/day or higher or equivalent) or immunosuppressive drugs within at least 2 weeks prior to the start of the study product.
3) Female patients who are pregnant, lactating, or planning to become pregnant during the study. In the case of male and female with the potential to become pregnant, those who do not agree to total abstinence (Sexual intercourse between individuals of different biological genders) during the study period and up to 14 days after the last dose of the study product. (The total abstinence, however, does not apply if bilateral fallopian tube occlusion or partner vasectomy has already been performed on a patient before obtaining consent for this study.)
4) Patients with active autoimmune disease requiring systemic or immunosuppressive therapy with corticosteroids or biologic agents.
5) Patients who have experienced immune-related adverse events with immune checkpoint inhibitors.
6) Patients with poorly controlled diabetes mellitus.
7) Patients with severe or more severe lung disease (mMRC Breathlessness Scale Grade 2 or higher) or with a history of non-infectious interstitial lung disease requiring steroid treatment.
8) Patients with significant cardiac disease (NYHA class III or greater).
9) Patients with concurrent multiple cancers or patients who underwent aggressive treatment within 2 years prior to the first dose of study treatment. Radically resected basal cell carcinoma or squamous cell carcinoma of the skin, radically resected non-invasive mammary ductal carcinoma or non-invasive breast cancer, and radically resected upper gastrointestinal carcinoma by endoscope were excluded.
10) Patients who are unable to use contrast media.
11) Patients with a history of hypersensitivity to human serum albumin products or proteins of foreign origin.
12) Patients who, at the time of consent acquisition, are participating in other clinical trials or clinical studies and are receiving other investigational products or are judged by the investigator or sub-investigator to have residual effects of adverse events caused by such products.
13)The genotypes of HLA-A, B and C are completely identical to those of the investigational product.
14) Patients with contraindications to leukapheresis (unstable angina, A-V block II degree or higher, WPW syndrome, complete left bundle branch block, systolic blood pressure below 90 or above 170 torr).
15) Patients who are judged by the attending physician to be unsuitable to participate in the study.
20age old over
80age old not
Both
Recurrent or advanced head and neck cancer
Injection of iPS-NKT cell and DC/Gal
Incidence of dose-limiting toxicity (DLT)
Response rate (RECIST ver.1.1)
Disease control rate (RECIST ver.1.1)
Occurrence of adverse events (type, frequency, severity, etc.)
Changes in clinical laboratory values
Changes of iPS-NKT cell count in the peripheral blood
Immune cell fraction in the peripheral blood
Omics analysis of peripheral blood immune cells
