Clinical Trials /

GFRα4 CAR T Cells in MTC Patients

NCT04877613

Description:

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells expressing a single-chain scFv targeting GFRα4 with tandem TCR/CD3ζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-GFRa4 cells") in patients with incurable medullary thyroid cancer (MTC).

Related Conditions:
  • Thyroid Gland Medullary Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: GFRα4 CAR T Cells in MTC Patients
  • Official Title: Phase I Trial of GFRα4 CAR T Cells in Adult Patients With Recurrent or Metastatic Medullary Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB# 848848; UPCC# 12320
  • NCT ID: NCT04877613

Conditions

  • Metastatic Medullary Thyroid Cancer

Interventions

DrugSynonymsArms
single dose of CART-GFRa4 cellsCohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusion
FludarabineCohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusion
CyclophosphamideCohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusion

Purpose

This is an open-label phase 1 study to assess the safety and feasibility of autologous T cells expressing a single-chain scFv targeting GFRα4 with tandem TCR/CD3ζ and 4-1BB (TCRζ/4-1BB) co-stimulatory domains (referred to as "CART-GFRa4 cells") in patients with incurable medullary thyroid cancer (MTC).

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: single dose of 5x10^7 CART-GFRa4 cells via intravenous infusionExperimental
  • single dose of CART-GFRa4 cells
  • Fludarabine
  • Cyclophosphamide
Cohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusionExperimental
  • single dose of CART-GFRa4 cells
  • Fludarabine
  • Cyclophosphamide
Cohort 2: single dose of 1x10^8 CART-GFRa4 cells via intravenous infusionExperimental
  • single dose of CART-GFRa4 cells
  • Fludarabine
  • Cyclophosphamide
Cohort 3: single fixed dose of 3x10^8 CART-GFRa4 cells via intravenous infusionExperimental
  • single dose of CART-GFRa4 cells
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. Signed, written informed consent

          2. Male or female age ≥ 18 years

          3. Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC).

          4. Incurable recurrent/metastatic disease that is progressive after at least 1 prior
             tyrosine kinase inhibitor (TKI) containing regimen, or the patient was intolerant of
             or declined such therapy.

          5. Adequate organ function defined as:

               1. Serum creatinine ≤ 2.5 mg/dl or estimated creatinine clearance ≥ 30 ml/min and
                  not on dialysis.

               2. AST ≤ 5x upper limit of normal range and total bilirubin ≤ 2.0 mg/dl; except for
                  patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome.

               3. Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA

               4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and
                  pulse oxygen > 92% on room air

          6. ECOG Performance Status that is either 0 or 1.

          7. Toxicities from prior therapies must have recovered to grade ≤ 2 according to the
             CTCAE 5.0 criteria or to the patient's prior baseline.

          8. Patients must have evaluable disease as defined by RECIST 1.1.

          9. Subjects of reproductive potential must agree to use acceptable birth control methods.

        Exclusion Criteria:

          1. Active hepatitis B or hepatitis C infection.

          2. Any other active, uncontrolled infection.

          3. Any prior history of moderate to severe (Grade 2 or higher) pneumonitis.

          4. Subjects with chronic kidney disease with Grade 2 or higher renal impairment (eGFR or
             CrCl 59-30 ml/min/1.73 m2).

          5. Class III/IV cardiovascular disability according to the New York Heart Association
             Classification.

          6. Clinically apparent arrhythmia or arrhythmias that are not stable on medical
             management within two weeks of physician-investigator confirmation of eligibility.

          7. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be
             on a stable low dose of steroids (≤10mg equivalent of prednisone). Use of inhaled
             steroids is allowable. Corticosteroid treatment as anti-emetic prophylaxis on the day
             of lymphodepleting chemotherapy administration is allowed per institutional practice.

          8. Any moderate to severe skin rash or allergies requiring systemic treatment.

          9. Receipt of immune checkpoint inhibitors within 2 months prior to
             physician-investigator confirmation of eligibility.

         10. Pregnant or nursing (lactating) women.

         11. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to
             ≥ 10mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS
             or Parkinson's) will be excluded.

         12. Have any history of prior or active central nervous system (CNS) involvement (e.g.,
             leptomeningeal disease, parenchymal masses) with MTC. Screening for this (e.g., with
             lumbar puncture and/or brain MRI) is not required unless suspicious symptoms and/or
             radiographic findings are present. Subjects with calvarial metastatic disease that
             extends intracranially and involves the dura will be excluded, even if CSF is negative
             for MTC.

         13. Known seizure disorder or history of prior seizures requiring medication.

         14. History of allergy or hypersensitivity to study product excipients (human serum
             albumin, DMSO, and Dextran 40).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0.
Time Frame:15 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of manufacturing products that meet release criteria.
Time Frame:3 months
Safety Issue:
Description:
Measure:Number of subjects who have a response
Time Frame:12 months
Safety Issue:
Description:
Measure:Best Overall Response (BOR)
Time Frame:12 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:12 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:12 months
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:12 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

June 18, 2021