Study of AIC100 CAR T Cells in Relapsed/Refractory Thyroid Cancer
Anaplastic Thyroid Cancer, Relapsed/Refractory Poorly Differentiated Thyroid Cancer
About this trial
This is an interventional treatment trial for Anaplastic Thyroid Cancer focused on measuring AIC100, CAR T Cell, Anaplastic Thyroid Cancer, Poorly Differentiated Thyroid Cancer
Eligibility Criteria
Inclusion Criteria:
- Willing and able to participate in the study and provide written informed consent
- Be ≥ 18 years of age on the day of signing the ICF
Patients must have thyroid cancer that expresses ICAM-1 and that meets one of the following diagnoses:
- ATC BRAF wild-type at any stage, including newly diagnosed
- ATC BRAF mutant after failure of or inability to tolerate BRAF-specific therapy
- PDTC that has failed any of the following treatments: surgery RAI, chemotherapy, radiation therapy, and/or targeted therapies
- Measurable disease by CT or PET/CT per RECIST v1.1
- ECOG performance status 0 to 2 (see Appendix 2; Section 14.2)
- Life expectancy greater than 8 weeks
Adequate hepatic, renal, bone marrow, cardiac, and coagulation function, defined as the following:
- Estimated creatinine clearance ≥ 50 mL/minute
- ALT and AST ≤ 2.5 × upper limit of normal (ULN); patients with hepatic metastases, ALT and AST ≤ 5 × ULN
- Serum total bilirubin < 1.5 mg/dL unless the patient has known Gilbert's Syndrome, then total bilirubin ≤ 3 mg/dL
- Serum albumin ≥ 2.5 g/dL
- Hemodynamically stable and left ventricular ejection fraction ≥ 45%
- Hematological parameters
i. Absolute neutrophil count > 1000/µL without myeloid growth factor support for ≥ 1 week ii. Absolute lymphocyte count ≥ 100/µL iii. Platelet count ≥ 50 × 10e3/µL without platelet transfusion for ≥ 1 week iv. Hemoglobin concentration > 8 g/dL without red blood cell transfusion for ≥ 2 weeks
- Has met the minimum washout time for previous cancer treatments (Section 5.5.3) before undergoing apheresis or LDC, and in the Investigator's judgement, the patient is able to safely undergo the procedure
- Absolute lymphocyte count ≥100/mm3 prior to apheresis (incorporated into inclusion criterion #7)
- Females of reproductive potential (defines as all females physiologically capable of becoming pregnant) must agree to use 1 highly effective method of contraception and 1 additional effective method (as defined in Section 6.3 ) from at least 28 days before enrollment/apheresis and for at least 1 year after the infusion of AIC100 CAR T Cells.
- Females of reproductive potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test result at Screening
- Detectable ICAM-1 expression by IHC (incorporated into inclusion criterion #3)
Exclusion Criteria:
- Women who are pregnant or breastfeeding
Clinically significant, active, uncontrolled, systemic infection; the following are not exclusionary:
- Patients with HIV must have been on effective antiretroviral therapy for ≥ 4 weeks prior to enrollment; must have an HIV viral load < 400 copies/µL; no acquired immunodeficiency syndrome related opportunistic infections in the previous 12 months; and a CD4+ cell count ≥ 350 cells/µL
- Patients with chronic HBV infection must on antiviral therapy and have an HBV viral load below the limits of detection
- Patients with chronic HCV infection must have completed therapy and have an HCV viral load below the limits of detection
- Prior treatment with investigational gene therapy or CAR T cell therapy
- Presence of active and clinically relevant central nervous system disorder such as epilepsy, stroke, or symptomatic or uncontrolled brain metastases
- Evidence of another malignancy within 2 years prior to Screening (except in-situ non melanoma skin cancers, localized controlled prostate cancer, adequately treated Stage 1 uterine cancer that has a low risk of recurrence, or any other malignancies with similar outcome)
- Patients who are seropositive for HIV or who have an uncontrolled HBV or HCV infection (incorporated into exclusion criterion #2)
- Active autoimmune disease (including but not limited to systemic lupus erythematosus, Sjögren's Syndrome, RA, psoriasis, multiple sclerosis, inflammatory bowel disease) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation, with the exception of conditions requiring thyroid replacement therapy
- Patients with severe chronic diseases of the kidney, liver, heart, lung; or any other serious illness that, in the opinion of the Investigator, may affect the patient's treatment, follow up, or assessments, including but not limited to uncontrolled clinically significant neurological or psychiatric disorders or metabolic diseases
- Patients who need long-term use of systemic corticosteroids > 10 mg/day prednisone or equivalent
- Allergy to any of the chemotherapy drugs given during lymphodepletion or known hypersensitivity to any component of AIC100 CAR T Cells, including excipients (Section 7.1)
- Receipt of a COVID-19 vaccine within 4 weeks before Screening
Sites / Locations
- City of Hope National Medical Center, City of Hope Medical CenterRecruiting
- Northwestern Memorial HospitalRecruiting
- Weill Cornell Medical College
- MD Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort -1
Cohort 1
Cohort 2
Cohort 3
Cohort 2.5
Cohort 4
AIC100 CAR T Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells
AIC100 CAR T Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells
AIC100 CAR T Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells
AIC100 CAR T Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR T cells
AIC100 CAR T Cell Dose Level 2.5 (Flat Dose): 2.5 x 10e8 CAR T cells. The interim step-down dose of Cohort 2.5 may be evaluated, if needed, based on ongoing safety and efficacy data.
AIC100 CAR T Cell Dose Level 4 (Flat Dose): 7.5 x 10e8 CAR T cells. The proposed escalation dose of Cohort 4 may be evaluated, if needed, based on ongoing safety and efficacy data.