This study is currently recruiting participants.
Number
16-C-0154
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women;Children
Keywords
Immunotherapy; Human Papillomavirus; Vulvar Intraepithelial Neoplasia; Vulvar High Grade Squamous Intraepithelial Lesion; Vaccine; HPV-related Malignancy; HPV-related Carcinoma; HPV-related Cervical Carcinoma; HPV-related Anal Squamous Cell Carcinoma; HPV Positive Oropharyngeal Squamous Cell Cancer
Recruitment Keyword(s)
None
Condition(s)
Papillomavirus Infections; Cervical Intraepithelial Neoplasia; Carcinoma In Situ; Vulvar Neoplasms; Vulvar Diseases
Investigational Drug(s)
E7 Transducted PBL Fludarabine
Investigational Device(s)
Intervention(s)
Biological/Vaccine: E7 TCR cells Drug: Aldesleukin Drug: Fludarabine Drug: Cyclophosphamide
Supporting Site
National Cancer Institute
Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have a HPV protein called E7 inside of their cells. In this new therapy, researchers take a person s blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 TCR cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people.
Objective:
To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients.
Eligibility:
Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal.
Design:
Participants will list all their medicines.
Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein.
Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.
The cells will be changed in the lab.
Participants will stay in the hospital. Over several days, they will get:
Chemotherapy drugs
E7 TCR cells
Shots or injections to stimulate the cells
Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests.
Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays.
Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis.
Participants will be followed for 15 years.
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INCLUSION CRITERIA: 1. Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by in situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test). 2. Patients must be HLA-A*02 by low resolution typing, and HLA-A*02:01 by one of the high resolution type results. 3. All patients must have received prior first line standard therapy or declined standard therapy. 4. Patients with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Patients with surgically resected brain metastases are eligible. 5. Greater than or equal to 18 years of age. 6. Able to understand and sign the Informed Consent Document. 7. Clinical performance status of ECOG 0 or 1. 8. Patients of both genders must be willing to practice birth control from the time of enrollment on this study up to four months after treatment. Patients must be willing to undergo testing for HPV-16 prior to becoming pregnant after this period. 9. Women of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. Women of childbearing potential are defined as all women except women who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least one year. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR transduced PBL, breastfeeding should be discontinued if the mother is treated with E7 TCR transduced PBL. These potential risks may also apply to other agents used in this study. 10. 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 are 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 the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. a. Hematology: - Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim. - WBC greater than or equal to 3000/mm^3 - Platelet count greater than or equal to 100,000/mm^3 - Hemoglobin > 8.0 g/dL b. Chemistry: - Serum ALT/AST less than or equal to 2.5 times the upper limit of normal - Calculated creatinine clearance (CCr) greater than or equal to 50 mL/min/1.73^2 using the Cockcroft-Gault equation - Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL c. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells. Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to Grade 1 or less. EXCLUSION CRITERIA: 1. Active systemic infections (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, severe obstructive or restrictive pulmonary disease. Patients with abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible. 2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 3. 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). 4. Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupus erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not exclusionary. 5. Patients on immunosuppressive drugs including corticosteroids. With the exception of: intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) -Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent; or, -Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine or aldesleukin. 7. Patients with a history of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test. 8. Documented LVEF of less than or equal to 45% tested. The following patients will undergo cardiac evaluations a. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or b. Age greater than or equal to 50 years old 9. Any other condition, which would, in the opinion of the Principal Investigator, indicate that the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained. 10. Subjects with baseline screening pulse oxygen level of < 95% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated
1. Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by in situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test).
2. Patients must be HLA-A*02 by low resolution typing, and HLA-A*02:01 by one of the high resolution type results.
3. All patients must have received prior first line standard therapy or declined standard therapy.
4. Patients with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Patients with surgically resected brain metastases are eligible.
5. Greater than or equal to 18 years of age.
6. Able to understand and sign the Informed Consent Document.
7. Clinical performance status of ECOG 0 or 1.
8. Patients of both genders must be willing to practice birth control from the time of enrollment on this study up to four months after treatment. Patients must be willing to undergo testing for HPV-16 prior to becoming pregnant after this period.
9. Women of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. Women of childbearing potential are defined as all women except women who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least one year. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR transduced PBL, breastfeeding should be discontinued if the mother is treated with E7 TCR transduced PBL. These potential risks may also apply to other agents used in this study.
10. 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 are 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 the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
a. Hematology:
- Absolute neutrophil count greater than 1000/mm^3 without the support of
filgrastim.
- WBC greater than or equal to 3000/mm^3
- Platelet count greater than or equal to 100,000/mm^3
- Hemoglobin > 8.0 g/dL
b. Chemistry:
- Serum ALT/AST less than or equal to 2.5 times the upper limit of normal
- Calculated creatinine clearance (CCr) greater than or equal to 50 mL/min/1.73^2 using the Cockcroft-Gault equation
- Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL
c. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells.
Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to Grade 1 or less.
EXCLUSION CRITERIA:
1. Active systemic infections (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, severe obstructive or restrictive pulmonary disease. Patients with abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible.
2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
3. 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).
4. Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupus erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not exclusionary.
5. Patients on immunosuppressive drugs including corticosteroids. With the exception of: intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
-Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent;
or,
-Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine or aldesleukin.
7. Patients with a history of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test.
8. Documented LVEF of less than or equal to 45% tested. The following patients will undergo cardiac evaluations
a. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or
b. Age greater than or equal to 50 years old
9. Any other condition, which would, in the opinion of the Principal Investigator, indicate that the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained.
10. Subjects with baseline screening pulse oxygen level of < 95% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated
Principal Investigator
Referral Contact
For more information: