Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing Human Thyroglobulin to People With Thyroglobulin Expressing Thyroid Cancer

NCT02390739 | Withdrawn Phase 1

• 2 other identifiers: 15009015-C-0090
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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: \<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.

Conditions

Metastatic Thyroid Cancer

Keywords

Immunotherapy; Gene Therapy; Metastatic Cancer

Outcome Measures

Primary Outcomes (1)

• Determine a safe dose of administration and determine if this approach will result in an objective tumor regression.

  Approximately 4 years

Study Arms (1)

Single Arm

EXPERIMENTAL

All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by antithyroglobulin mTCR PBL and aldesleukin.

Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Anti-Thyroglobulin mTCR PBL

Interventions

Aldesleukin DRUG

Aldeskeukin 720,000 IU/kg IV over 15 minutes approximately every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum of 9 doses).

Single Arm

Fludarabine DRUG

Day -7 to -3:Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Single Arm

Cyclophosphamide DRUG

Days -7 and -6:Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hour.

Single Arm

Anti-Thyroglobulin mTCR PBL BIOLOGICAL

On day 0, one to four days after last dose of fludarabine, cells will be infused intravenously (IV) over 20 to 30 minutes.

Single Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unresectable thyroid cancer expressing TG as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue.
• 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.
• Confirmation of diagnosis of thyroid cancer by the Laboratory of Pathology of the NCI.
• PET avid disease with SUV \>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.
• 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.
• Greater than or equal to 18 years of age and less than or equal to 70 years of age.
• Willing to sign a durable power of attorney
• Able to understand and sign the Informed Consent Document
• Clinical performance status of ECOG 0 or 1
• Life expectancy of greater than three months
• Patients must be HLA-A\*0201 positive
• 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.
• 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.)

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Any form of primary immunodeficiency (such as Severe Combined
• Immunodeficiency Disease).
• 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.
• 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).
• Concurrent systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.
• History of coronary revascularization or ischemic symptoms
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Related Publications (3)

• Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan;63(1):11-30. doi: 10.3322/caac.21166. Epub 2013 Jan 17.

  PMID: 23335087 BACKGROUND

• Castro MR, Bergert ER, Goellner JR, Hay ID, Morris JC. Immunohistochemical analysis of sodium iodide symporter expression in metastatic differentiated thyroid cancer: correlation with radioiodine uptake. J Clin Endocrinol Metab. 2001 Nov;86(11):5627-32. doi: 10.1210/jcem.86.11.8048.

  PMID: 11701745 BACKGROUND

• Droz JP, Schlumberger M, Rougier P, Ghosn M, Gardet P, Parmentier C. Chemotherapy in metastatic nonanaplastic thyroid cancer: experience at the Institut Gustave-Roussy. Tumori. 1990 Oct 31;76(5):480-3. doi: 10.1177/030089169007600513.

  PMID: 2256195 BACKGROUND

MeSH Terms

Conditions

Thyroid Neoplasms; Neoplasm Metastasis

Interventions

aldesleukin; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• James C Yang, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 18, 2015
• Study Start: March 2, 2015
• Primary Completion: March 22, 2017
• Study Completion: March 22, 2017
• Last Updated: December 16, 2019

Record last verified: 2017-03-22