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Study of AIC100 CAR T Cells in Relapsed/Refractory Thyroid Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04420754
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : February 13, 2023
Sponsor:
Information provided by (Responsible Party):
AffyImmune Therapeutics, Inc.

Brief Summary:
The purpose of this study is to assess the safety and tolerability and determine the recommended Phase 2 dose of AIC100 Chimeric Antigen Receptor (CAR) T cells in patients with relapsed/refractory poorly differentiated thyroid cancer and anaplastic thyroid cancer.

Condition or disease Intervention/treatment Phase
Anaplastic Thyroid Cancer Relapsed/Refractory Poorly Differentiated Thyroid Cancer Biological: AIC100 CAR T Cells Phase 1

Detailed Description:

The primary objective of this study is to assess the safety and tolerability of AIC100 CAR T Cells and determine the recommended Phase 2 dose of AIC100 in patients with relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic thyroid cancer that are BRAF wild-type, including newly diagnosed, or BRAF mutant anaplastic thyroid cancer after failure of BRAF mutant specific therapy.

Upon enrollment, patients will undergo apheresis for collection of autologous lymphocytes. The autologous T cells will be transfected and expanded in-vitro to generate the AIC100 CAR T Cell product. After lymphodepleting chemotherapy, AIC100 will be infused.

The study drug, AIC100, consists of autologous CAR T cells targeting intercellular adhesion molecule-1 (ICAM-1) on thyroid cancer. In addition, AIC100 cells express the somatostatin receptor subtype 2 (SSTR2), which should enable CAR T cell imaging in the patient.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase I Study of AIC100 CAR T Cells in Relapsed and/or Refractory Advanced Thyroid Cancer or Anaplastic Thyroid Cancer
Actual Study Start Date : September 28, 2020
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Thyroid

Arm Intervention/treatment
Experimental: Cohort -1
AIC100 CAR T Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells
Biological: AIC100 CAR T Cells
Autologous CAR T cells directed against ICAM-1
Other Name: AIC100

Experimental: Cohort 1
AIC100 CAR T Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells
Biological: AIC100 CAR T Cells
Autologous CAR T cells directed against ICAM-1
Other Name: AIC100

Experimental: Cohort 2
AIC100 CAR T Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells
Biological: AIC100 CAR T Cells
Autologous CAR T cells directed against ICAM-1
Other Name: AIC100

Experimental: Cohort 3
AIC100 CAR T Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR T cells
Biological: AIC100 CAR T Cells
Autologous CAR T cells directed against ICAM-1
Other Name: AIC100




Primary Outcome Measures :
  1. Incidence of overall Grade >=3 Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: Up to 15 years post-infusion ]
    The number of Grade 3, 4 and 5 AEs and SAEs that occur throughout the study.

  2. Incidence of anticipated AIC100 CAR T Cell related AEs, SAEs and adverse events of special interest (AESI) [ Time Frame: Up to 15 years post-infusion ]
    The number of CAR T related adverse events that occur throughout the study, including AESIs, infusion-related reactions, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), tumor lysis syndrome (TLS) and new malignancies.


Secondary Outcome Measures :
  1. Expansion and Persistence of AIC100 CAR transgenes after infusion [ Time Frame: Up to 15 years post-infusion ]
    Number of AIC100 cells present after infusion by polymerase chain reaction (PCR)

  2. Analysis of AIC100 CAR T Cell Subsets by Flow Cytometry in Peripheral Blood [ Time Frame: Up to 15 years post-infusion ]
    Measurement of CAR T cell subsets by flow cytometry in peripheral blood

  3. Assessment and Analysis of CAR T cell infiltrate in tumor by biopsy [ Time Frame: 42 days post-infusion ]
    Comparison of tumor biopsies collected prior to infusion of AIC100 therapy and at the end of treatment and/or progression to assess cellular infiltrate and immune profiling.

  4. Cytokine levels in serum samples [ Time Frame: 42 days post-infusion ]
    Measurement of cytokine levels in serum samples by enzyme-linked immunosorbent assay (ELISA) to evaluate correlation with CAR T levels and with clinical tumor response

  5. Anti-CAR antibodies in peripheral blood [ Time Frame: Up to 1 year post-infusion ]
    Assessment and measurement of CAR T antibodies in peripheral blood post-infusion



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to participate in the study and provide written informed consent
  2. Be ≥ 18 years of age on the day of signing the ICF
  3. Patients must have thyroid cancer that expresses ICAM-1 and that meets one of the following diagnoses:

    1. ATC BRAF wild-type at any stage, including newly diagnosed
    2. ATC BRAF mutant after failure of or inability to tolerate BRAF-specific therapy
    3. PDTC that has failed any of the following treatments: surgery RAI, chemotherapy, radiation therapy, and/or targeted therapies
  4. Measurable disease by CT or PET/CT per RECIST v1.1
  5. ECOG performance status 0 to 2 (see Appendix 2; Section 14.2)
  6. Life expectancy greater than 8 weeks
  7. Adequate hepatic, renal, bone marrow, cardiac, and coagulation function, defined as the following:

    1. Estimated creatinine clearance ≥ 50 mL/minute
    2. ALT and AST ≤ 2.5 × upper limit of normal (ULN); patients with hepatic metastases, ALT and AST ≤ 5 × ULN
    3. Serum total bilirubin < 1.5 mg/dL unless the patient has known Gilbert's Syndrome, then total bilirubin ≤ 3 mg/dL
    4. Serum albumin ≥ 2.5 g/dL
    5. Hemodynamically stable and left ventricular ejection fraction ≥ 45%
    6. 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

  8. 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
  9. Absolute lymphocyte count ≥100/mm3 prior to apheresis (incorporated into inclusion criterion #7)
  10. 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.
  11. Females of reproductive potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test result at Screening
  12. Detectable ICAM-1 expression by IHC (incorporated into inclusion criterion #3)

Exclusion Criteria:

  1. Women who are pregnant or breastfeeding
  2. Clinically significant, active, uncontrolled, systemic infection; the following are not exclusionary:

    1. 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
    2. Patients with chronic HBV infection must on antiviral therapy and have an HBV viral load below the limits of detection
    3. Patients with chronic HCV infection must have completed therapy and have an HCV viral load below the limits of detection
  3. Prior treatment with investigational gene therapy or CAR T cell therapy
  4. Presence of active and clinically relevant central nervous system disorder such as epilepsy, stroke, or symptomatic or uncontrolled brain metastases
  5. 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)
  6. Patients who are seropositive for HIV or who have an uncontrolled HBV or HCV infection (incorporated into exclusion criterion #2)
  7. 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
  8. 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
  9. Patients who need long-term use of systemic corticosteroids > 10 mg/day prednisone or equivalent
  10. 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)
  11. Receipt of a COVID-19 vaccine within 4 weeks before Screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04420754


Contacts
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Contact: Sonal Gupta, MD PhD 508-654-3600 ext 3 sgupta@affyimmune.com
Contact: Dawn Buchanan 508-654-3600 ext 5 dbuchanan@affyimmune.com

Locations
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United States, California
City of Hope National Medical Center, City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Victoria Villaflor, MD    800-826-4673    vvillaflor@coh.org   
Principal Investigator: Victoria Villaflor, MD         
United States, New York
Weill Cornell Medical College Active, not recruiting
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Shehanie Brana, RN    713-563-4406    SHBrana@mdanderson.org   
Principal Investigator: Samer Srour, MB ChB         
Sub-Investigator: Maria E Cabanillas, MD         
Sub-Investigator: Mark Zafereo, MD, FACS         
Sponsors and Collaborators
AffyImmune Therapeutics, Inc.
Investigators
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Study Director: Sonal Gupta, MD PhD AffyImmune Therapeutics, Inc.
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Responsible Party: AffyImmune Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04420754    
Other Study ID Numbers: 19-12021154
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: February 13, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AffyImmune Therapeutics, Inc.:
AIC100
CAR T Cell
Anaplastic Thyroid Cancer
Poorly Differentiated Thyroid Cancer
Additional relevant MeSH terms:
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Thyroid Neoplasms
Thyroid Carcinoma, Anaplastic
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type