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Study of AIC100 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 : September 25, 2020
Sponsor:
Collaborator:
Weill Medical College of Cornell University
Information provided by (Responsible Party):
AffyImmune Therapeutics, Inc.

Brief Summary:
The purpose of this study is to assess the safety and determine the recommended 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 determine the recommended dose of AIC100 for phase II study in patients with relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic thyroid cancer that are BRAF wild-type, or BRAF mutant anaplastic thyroid cancer after failure of BRAF-mutant specific therapy.

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

The study drug, AIC100, consists of autologous CAR T cells containing the I domain of lymphocyte function-associated antigen-1 (LFA-1) and targeting its over-expressed physiological ligand, intercellular adhesion molecule-1 (ICAM-1) on thyroid cancer. AIC100 cells also express the transmembrane domain of CD8 alpha and intracellular domains of the co-stimulatory receptors CD28 and 41BB, and the cytoplasmic signaling domain of the T cell receptor associated CD3. In addition, AIC100 cells express the somatostatin receptor subtype 2 (SSTR2), which should enable CAR T cell imaging in the patient.

The treatment with AIC100 is a single dose infusion. However, additional infusions may be administered if the following conditions are met: (1) patient shows stable disease or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after 30 days, (2) the investigator has deemed it is in the best interest of the patient, (3) patient did not experience a dose limiting toxicity (DLT), and (4) there are cell doses available from the already manufactured cell product. The cell dose for subsequent infusions will be similar to that of the initial dose. In individual cases and only with the explicit approval of the Data and Safety Monitoring Board (DSMB) and Food and Drug Administration (FDA), a higher dose could be administered. This would typically be justified by efficacy and toxicity data generated in other participants. Prior to additional infusions, lymphodepleting chemotherapy will be repeated.

Enrollment will be staggered so that each patient will be followed for at least 30 days prior to enrollment of the next patient for the initial Dose 1 cohort. This is a dose escalation study using cohorts of 3 patients. Patients will receive a flat dose of 1 x 10e7, 1 x 10e8 or 5 x 10e8 viable CAR T cells with a dose -1 Cohort of 1 x 10e6

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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 Multi Center Phase I Study of AIC100 in Relapsed and/or Refractory Advanced Thyroid Cancer and Anaplastic Thyroid Cancer
Estimated Study Start Date : September 28, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Thyroid

Arm Intervention/treatment
Experimental: Cohort -1
AIC100 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 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 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 Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR Tcells
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 - 5 Adverse Events [ Time Frame: 42 days post-infusion ]
    The number of Grade 3, 4 and 5 adverse events that occur throughout the study.

  2. Incidence of CAR T-related Adverse Effects [ Time Frame: 42 days post-infusion ]
    The number of CAR T related adverse effects that occur throughout the study, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) and tumor lysis syndrome (TLS)


Secondary Outcome Measures :
  1. Detection, Expansion and Persistence of AIC100 cells 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 CAR T 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 CART cell infiltrate in tumor by biopsy at completion of treatment and/or progression. [ Time Frame: 42 days post-infusion ]
    Comparison of tumor biopsies collected prior to initiation of AIC100 therapy and at the end of treatment and/or progression to assess cellular infiltrate and immune profiling.

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

  5. CAR T Antibodies in peripheral blood [ Time Frame: Up to 15 years 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. One of the following thyroid malignancies:

    1. Anaplastic Thyroid Cancer (ATC), BRAF wild-type at any stage including newly diagnosed.
    2. Anaplastic Thyroid Cancer (ATC) BRAF mutant after failure of BRAF specific therapy.
    3. Poorly differentiated thyroid cancer that has failed surgery, radioactive iodine, chemotherapy, radiation therapy and/or targeted therapies.
  3. Measurable disease (by Computed Tomography [CT] scan or Positron Emission Tomography/Computed Tomography [PET/CT])
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
  5. Life expectancy of greater than 8 weeks.
  6. Adequate hepatic, renal, bone marrow, and coagulation function defined as:

    1. Estimated creatinine clearance >= 60 ml/min
    2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x the upper limit of normal (ULN); subjects with hepatic metastases ALT and AST <= 3.0 x ULN
    3. Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome, then serum bilirubin <= 3 mg/dL
    4. Serum albumin >= 3.0 g/dL
  7. Has recovered by toxicity or prior anticancer therapy to Grade 0-1
  8. Absolute lymphocyte count (ALC) >= 300/mm3 prior to apheresis
  9. Females of reproductive potential must agree to use one highly effective method of contraception and one additional effective method from at least 28 days prior to beginning study therapy, during study therapy including dose interruptions, and for 1 year after the last dose of study therapy.
  10. Females of reproductive potential must have a negative serum beta human chorionic gonadotropin pregnancy test result at screening and within 48 hours prior to the first dose of study therapy.
  11. Detectable ICAM 1 expression on tumor by immunohistochemistry

Exclusion Criteria:

  1. Women who are pregnant or breastfeeding.
  2. Active systemic infections that are not controlled.
  3. Previous treatment with investigational gene therapy or chimeric antigen receptor therapy.
  4. Presence of active and clinically relevant central nervous system disorder such as epilepsy, stroke.
  5. Evidence of another malignancy within 2 years prior to Screening (except in situ non- melanoma skin cell cancers)
  6. Patients with seropositive response of human immunodeficiency virus (HIV) or uncontrolled hepatitis B virus or hepatitis C virus infections.
  7. Active autoimmune disease (including but not limited to: systemic lupus erythematous, Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to eligibility confirmation by investigator, with the exception of thyroid replacement.
  8. Patients with severe chronic diseases of kidney, liver, heart, lung. Patients with any other serious illnesses that the investigators consider it may affect the patient's treatments, follow-up or assessment, including any uncontrolled clinically significant neurological or psychiatric disorders, auto-immune disorders, metabolic diseases, infectious diseases and so on.
  9. Patients who need long-term use of systemic steroids.
  10. Allergy to any of the chemotherapy drugs given during lymphodepletion.

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: Ashlee Torres, RN 212-746-7117 ant9015@med.cornell.edu
Contact: June Greenberg, RN 212-746-2651 jdg2002@med.cornell.edu

Locations
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United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Ashlee Torres, RN    212-746-7117    ant9015@med.cornell.edu   
Principal Investigator: Koen van Besien, MD, PhD         
Sponsors and Collaborators
AffyImmune Therapeutics, Inc.
Weill Medical College of Cornell University
Investigators
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Principal Investigator: Koen van Besien, MD, PhD Weill Medical College of Cornell University
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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: September 25, 2020
Last Verified: September 2020
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
Advanced 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