Clinical Trials /

Study of AIC100 in Relapsed/Refractory Thyroid Cancer

NCT04420754

Description:

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.

Related Conditions:
  • Poorly Differentiated Thyroid Gland Carcinoma
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AIC100 in Relapsed/Refractory Thyroid Cancer
  • Official Title: A Multi Center Phase I Study of AIC100 in Relapsed and/or Refractory Advanced Thyroid Cancer and Anaplastic Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19-12021154
  • NCT ID: NCT04420754

Conditions

  • Anaplastic Thyroid Cancer
  • Thyroid Cancer

Interventions

DrugSynonymsArms
AIC100 CAR T CellsAIC100Cohort -1

Purpose

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.

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
    

Trial Arms

NameTypeDescriptionInterventions
Cohort -1ExperimentalAIC100 Cell Dose Level -1 (Flat Dose): 1 x 10e6 cells
  • AIC100 CAR T Cells
Cohort 1ExperimentalAIC100 Cell Dose Level 1 (Flat Dose): 1 x 10e7 cells
  • AIC100 CAR T Cells
Cohort 2ExperimentalAIC100 Cell Dose Level 2 (Flat Dose): 1 x 10e8 cells
  • AIC100 CAR T Cells
Cohort 3ExperimentalAIC100 Cell Dose Level 3 (Flat Dose): 5 x 10e8 cells
  • AIC100 CAR T Cells

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

Primary Outcome Measures

Measure:Incidence of overall Grade 3 - 5 Adverse Events
Time Frame:42 days post-infusion
Safety Issue:
Description:The number of Grade 3, 4 and 5 adverse events that occur throughout the study.

Secondary Outcome Measures

Measure:Detection, Expansion and Persistence of AIC100 cells after infusion
Time Frame:Up to 15 years post-infusion
Safety Issue:
Description:Number of AIC100 cells present after infusion by polymerase chain reaction (PCR)
Measure:Analysis of CAR T Subsets by Flow Cytometry in Peripheral Blood
Time Frame:Up to 15 years post-infusion
Safety Issue:
Description:Measurement of CAR T cell subsets by flow cytometry in peripheral blood
Measure:Assessment and Analysis of CART cell infiltrate in tumor by biopsy at completion of treatment and/or progression.
Time Frame:42 days post-infusion
Safety Issue:
Description: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.
Measure:Cytokine levels in plasma samples
Time Frame:42 days post-infusion
Safety Issue:
Description: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
Measure:CAR T Antibodies in peripheral blood
Time Frame:Up to 15 years post-infusion
Safety Issue:
Description:Assessment and measurement of CAR T antibodies in peripheral blood post-infusion

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Trial Keywords

  • AIC100
  • CAR T Cell
  • Anaplastic Thyroid Cancer
  • Advanced Thyroid Cancer

Last Updated

June 9, 2020