Metastatic Thyroid Cancer Clinical Trial
Official title:
Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to Patients With Thyroglobulin Expressing Thyroid Cancer
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:
<TAB>Adults 18 and older with thyroid cancer that has the thyroglobulin molecule on tumor
surfaces
Design:
<TAB>Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and
undergo a history and physical examination, scans, x-rays, lab tests, and other tests as
needed
<TAB>Leukapheresis: If the patients meet all of the requirements for the study they will
undergo leukapheresis to obtain white blood cells to make the anti- thyroglobulin cells.
{Leukapheresis is a common procedure, which removes only the white blood cells from the
patient.}
<TAB>Treatment: Once their cells have grown, the patients will be admitted to the hospital
for the conditioning chemotherapy, the anti-thyroglobulin cells and aldesleukin. They will
stay in the hospital for about 4 weeks for the treatment.
Follow up:
Patients will return to the clinic for a physical exam, review of side effects, lab tests,
and scans about every 1-3 months for the first year, and then every 6 months to 1 year as
long as their tumors are shrinking. Follow up visits take up to 2 days.
Background:
- We generated a murine T-cell receptor (mTCR) that recognizes human thyroglobulin (hTG)
in the context of HLA-A0201 and constructed a single retroviral vector that contains its
alpha and beta chains and will confer hTG recognition to HLA-A0201+ PBL on transduction.
- In co-cultures with HLA-A0201+, hTG+ target cells, anti-TG mTCR transduced T cells
secrete significant amounts of IFN- >= with high specificity.
Objectives:
Primary objectives:
- To determine the safety of administering PBL transduced with this anti-TG mTCR in
concert with preparative lymphodepletion and high dose interleukin-2 (IL-2;
aldesleukin).
- Determine if these mTCR-transduced PBL can mediate the regression of TG-expressing
tumors.
Eligibility:
Patients who are HLA-A*0201 positive and 18 years of age or older must have
-Advanced TG-expressing thyroid cancer (including those with bone-only disease) which has
progressed after surgery (if indicated) and radioiodine ablation
Patients may not have:
-Contraindications for high dose aldesleukin administration.
Design:
- PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and
aldesleukin in order to stimulate T-cell growth.
- Transduction is initiated by exposure of these cells to retroviral vector supernatant
containing replication-incompetent virus encoding the anti-TG mTCR.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide and fludarabine.
- On day 0 patients will receive their PBL transduced with the anti-TG mTCR and then begin
high dose aldesleukin.
- A complete evaluation of evaluable lesions will be conducted approximately 4-6 weeks
after treatment.
- The study will be conducted using a Phase I/II optimal design.
- The objective will be to determine if the combination of high dose aldesleukin,
lymphocyte depleting chemotherapy, and anti-TG mTCR-gene engineered lymphocytes is able
to be associated with a clinical response rate that can rule out 5% (p0=0.05) in favor
of a modest 20% PR + CR rate (p1=0.20).
- A total of up to 68 patients may be required; approximately 25 patients in the phase I
portion of the study and 43 (41, plus an allowance of up to 2 non-evaluable) patients in
the phase II portion of the study.
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