GFRα4 CAR T Cells in MTC Patients
Phase 1
Recruiting
- Conditions
- Metastatic Medullary Thyroid CancerRecurrent Thyroid Gland Medullary Carcinoma
- Interventions
- Registration Number
- NCT04877613
- Lead Sponsor
- University of Pennsylvania
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 18
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.
Read More
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).
Read More
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1: single dose of 5x10^7 CART-GFRa4 cells via intravenous infusion Cyclophosphamide - Cohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusion single dose of CART-GFRa4 cells - Cohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusion Fludarabine - Cohort -1: single dose of 2x10^7 CART-GFRa4 cells via intravenous infusion Cyclophosphamide - Cohort 1: single dose of 5x10^7 CART-GFRa4 cells via intravenous infusion single dose of CART-GFRa4 cells - Cohort 1: single dose of 5x10^7 CART-GFRa4 cells via intravenous infusion Fludarabine - Cohort 2: single dose of 1x10^8 CART-GFRa4 cells via intravenous infusion single dose of CART-GFRa4 cells - Cohort 2: single dose of 1x10^8 CART-GFRa4 cells via intravenous infusion Fludarabine - Cohort 2: single dose of 1x10^8 CART-GFRa4 cells via intravenous infusion Cyclophosphamide - Cohort 3: single fixed dose of 3x10^8 CART-GFRa4 cells via intravenous infusion single dose of CART-GFRa4 cells - Cohort 3: single fixed dose of 3x10^8 CART-GFRa4 cells via intravenous infusion Fludarabine - Cohort 3: single fixed dose of 3x10^8 CART-GFRa4 cells via intravenous infusion Cyclophosphamide -
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0. 15 years
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) 12 months Duration of Response (DOR) 12 months Percentage of manufacturing products that meet release criteria. 3 months Number of subjects who have a response 12 months Best Overall Response (BOR) 12 months Overall survival (OS) 12 months
Trial Locations
- Locations (1)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States