GFRα4 CAR T Cells in MTC Patients

Metastatic Medullary Thyroid Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04877613
• Other study ID #: IRB# 848848; UPCC# 12320
• Status: Recruiting
• Phase: Phase 1
• Start date: August 19, 2021
• Est. completion date: June 1, 2039

Study information

• Verified date: June 2023
• Source: University of Pennsylvania
• Contact: Abramson Cancer Center Clinical Trials Service
• Phone: 855-216-0098
• Email: PennCancerTrials[@]careboxhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: June 1, 2039
• Est. primary completion date: June 1, 2039
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Evidence of 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 - Retired with Protocol Version 3.

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).

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Metastatic Medullary Thyroid Cancer
• Thyroid Neoplasms

Intervention

Drug:
• single dose of CART-GFRa4 cells
Intravenous infusion of lentiviral transduced autologous T cells that have been engineered to express an extracellular single chain antibody (scFv) with specificity towards GFRa4 with fludarabine and cyclophosphamide.
• Fludarabine
Lyphodepletion
• Cyclophosphamide
Lyphodepletion

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0.		15 years
Secondary	Percentage of manufacturing products that meet release criteria.		3 months
Secondary	Number of subjects who have a response		12 months
Secondary	Best Overall Response (BOR)		12 months
Secondary	Duration of Response (DOR)		12 months
Secondary	Overall survival (OS)		12 months
Secondary	Progression-free survival (PFS)		12 months