Phase I Trial of GFRα4 CAR T Cells in Adult Patients With Recurrent or Metastatic Medullary Thyroid Cancer

  • STATUS
    Recruiting
  • End date
    Jun 1, 2039
  • participants needed
    18
  • sponsor
    University of Pennsylvania
Updated on 18 October 2022

Summary

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).

Details
Condition Metastatic Medullary Thyroid Cancer
Treatment cyclophosphamide, Fludarabine, single dose of CART-GFRa4 cells
Clinical Study IdentifierNCT04877613
SponsorUniversity of Pennsylvania
Last Modified on18 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Signed, written informed consent
Male or female age ≥ 18 years
Histologically or cytologically confirmed diagnosis of medullary thyroid cancer (MTC)
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
Adequate organ function defined as
Serum creatinine ≤ 2.5 mg/dl or estimated creatinine clearance ≥ 30 ml/min and not on dialysis
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
Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO/MUGA
Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
ECOG Performance Status that is either 0 or 1
Toxicities from prior therapies must have recovered to grade ≤ 2 according to the CTCAE 5.0 criteria or to the patient's prior baseline
Patients must have evaluable disease as defined by RECIST 1.1
Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

Evidence of active hepatitis B or hepatitis C infection
Any other active, uncontrolled infection
Any prior history of moderate to severe (Grade 2 or higher) pneumonitis
Subjects with chronic kidney disease with Grade 2 or higher renal impairment (eGFR or CrCl 59-30 ml/min/1.73 m2)
Class III/IV cardiovascular disability according to the New York Heart Association Classification
Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility
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
Any moderate to severe skin rash or allergies requiring systemic treatment
Receipt of immune checkpoint inhibitors within 2 months prior to physician-investigator confirmation of eligibility - Retired with Protocol Version 3
Pregnant or nursing (lactating) women
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
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
Known seizure disorder or history of prior seizures requiring medication
History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
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