Overview
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer
Status:
Withdrawn
Withdrawn
Trial end date:
2017-03-22
2017-03-22
Target enrollment:
0
0
Participant gender:
All
All
Summary
Background The NCI Surgery Branch has developed an experimental therapy for treating patient with metastatic thyroid cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-thyroglobulin incorporated in the retrovirus. Objectives: The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the thyroglobulin molecule on their surface can cause thyroid tumors to shrink and to see if this treatment is safe. Eligibility:Phase:
Phase 1/Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
National Cancer Institute (NCI)Treatments:
Aldesleukin
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Vidarabine
Criteria
- INCLUSION CRITERIA:1. Unresectable thyroid cancer expressing TG as assessed by one of the following
methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue.
2. Recurrent/metastatic radioiodine refractory disease that has progressed within
the past 6 months with at least 1 lesion increasing by 0.5cm in diameter or with
increasing bone metastases.
3. Confirmation of diagnosis of thyroid cancer by the Laboratory of Pathology of the
NCI.
4. PET avid disease with SUV >5.
5. Patients must have previously received standard systemic therapy for advanced
thyroid cancer (to include radioactive iodine for iodine-avid tumors and surgery
(if indicated)) and have been either non-responders (progressive disease) or have
recurred.
6. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and
asymptomatic are eligible. Lesions that have been treated with stereotactic
radiosurgery must be clinically stable for 1 month after treatment for the
patient to be eligible.
7. Greater than or equal to 18 years of age and less than or equal to 70 years of
age.
8. Willing to sign a durable power of attorney
9. Able to understand and sign the Informed Consent Document
10. Clinical performance status of ECOG 0 or 1
11. Life expectancy of greater than three months
12. Patients must be HLA-A*0201 positive
13. Patients of both genders must be willing to practice birth control from the time
of enrollment on this study and for up to four months after treatment.
14. Serology:
- Seronegative for HIV antibody. (The experimental treatment being evaluated in this
protocol depends on an intact immune system. Patients who are HIV seropositive can
have decreased immune-competence and thus be less responsive to the experimental
treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If
hepatitis C antibody test is positive, then patient must be tested for the presence of
antigen by RT-PCR and be HCV RNA negative.
o. Women of child-bearing potential must have a negative pregnancy test because of the
potentially dangerous effects of the treatment on the fetus.
p. Hematology
- Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
- WBC less than or equal to 3000/mm3
- Platelet count greater than or equal to 100,000/mm3
- Hemoglobin greater than 8.0 g/dl
q. Chemistry:
- Serum ALT/AST less than or equal to to 2.5 times the upper limit of normal
- Serum creatinine less than or equal to to 1.6 mg/dl
- Total bilirubin less than or equal to to 1.5 mg/dl, except in patients with Gilbert s
Syndrome who must have a total bilirubin less than 3.0 mg/dl.
r. More than four weeks must have elapsed since any prior systemic therapy at the time
the patient receives the preparative regimen, and patients toxicities must have
recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as
long as all toxicities have recovered to grade 1 or less.
EXCLUSION CRITERIA:
1. Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the treatment on the fetus or infant.
2. Any form of primary immunodeficiency (such as Severe Combined
Immunodeficiency Disease).
3. Active systemic infections (e.g. : requiring anti-infective treatment), coagulation
disorders or other major medical illnesses of the cardiovascular, respiratory or
immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive
pulmonary disease.
4. Concurrent opportunistic infections (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who have decreased immune
competence may be less responsive to the experimental treatment and more susceptible
to its toxicities).
5. Concurrent systemic steroid therapy.
6. History of severe immediate hypersensitivity reaction to cyclophosphamide or
fludarabine.
7. History of coronary revascularization or ischemic symptoms
8. Documented LVEF of less than or equal to 45%. Testing is required in patients with:
- Clinically significant atrial and/or ventricular arrhythmias including but not
limited to: atrial fibrillation, ventricular tachycardia, second or third degree
heart block
- Age greater than or equal to 60 years old