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Protocol Details

A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for Human Papillomavirus-Associated Cancers

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

12-C-0116

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 66

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Immunotherapy;
HPV-Associated Cancers;
Cervical Cancer;
Oropharyngeal Cancer;
HPV Infection

Recruitment Keyword(s)

None

Condition(s)

Cervical Cancer;
Oropharyngeal Cancer;
Vaginal Cancer;
Anal Cancer;
Penile Cancer

Investigational Drug(s)

Young TIL

Investigational Device(s)

None

Intervention(s)

Drug: Fluderabine
Drug: Cycolphosphamide
Biological/Vaccine: Young TIL
Biological/Vaccine: Aldesleukin

Supporting Site

National Cancer Institute

Background:

- The human papillomavirus (HPV) can cause a number of cancers, including cervical and throat cancers. One experimental treatment for these cancers involves surgery to remove a piece or all of a tumor from one area of cancer. The white blood cells that are attacking the cancer are grown from the tumor in the laboratory then given back to the same patient to treat the remaining cancer. In this protocol the cells are given with the drug aldesleukin, which helps the cells stay alive and kill tumors.

Objectives:

- To see if white blood cells from the patient s own tumor given with aldesleukin is a safe and effective treatment for HPV-related cancer.

Eligibility:

- Individuals at least 18 years and less than or equal to 66 years of age who have a type of cancer that is associated with HPV.

Design:

- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.

- Surgery or biopsy will be performed to obtain tumor from which to grow white blood cells. White blood cells will be grown from the tumor in the laboratory.

- Participants will have leukapheresis to collect additional white blood cells.

- Participants will have one week of chemotherapy to prepare their immune system to accept the white blood cells.

- Participants will receive an infusion of their own white blood cells grown from tumor. They will also receive aldesleukin for up to five days to boost the immune system s response to the white blood cells. They will remain in the hospital until they have recovered from the treatment.

- Participants will have frequent follow-up visits to monitor the outcome of the treatment.

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Eligibility

INCLUSION CRITERIA:

a. Measurable metastatic or locally advanced refractory/recurrent malignancies that are high-risk HPV positive by in situ hybridization (ISH) or polymerase chain reaction (PCR) or any cancer from the uterine cervix.

b. All patients must have received prior platinum-based chemotherapy or chemoradiotherapy.

c. Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.

d. Greater than or equal to 18 years of age and less than or equal to age 66.

e. Able to understand and sign the Informed Consent Document

f. Clinical performance status of ECOG 0 or 1.

g. Life expectancy of greater than three months

h. 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 receiving the preparative regimen.

i. 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.

- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.

j. 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/mm3

- Hemoglobin > 8.0 g/dl

k. Chemistry:

- Serum ALT/AST less than or equal to 2.5 times the upper limit of normal

- Serum creatinine less than or equal to 1.6 mg/dl

- 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.

l. 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:

a. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy treatment on the fetus or infant.

b. Active systemic infections, 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 arrhythimas, obstructive or restrictive pulmonary disease.

c. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

d. 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).

e. Concurrent systemic steroid therapy.

f. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

g. History of coronary revascularization or ischemic symptoms.

h. Any patient known to have an LVEF less than or equal to 45%.

i. Documented LVEF of less than or equal to 45% tested in patients with i) clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or ii) age greater than or equal 60 years old.

j. Documented FEV1 less than or equal to 60% of predicted tested in patients with i) a prolonged history of cigarette smoking (20pk/ year of smoking within the past 2 years) or ii) symptoms of respiratory dysfunction.


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Citations:

Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol.

Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res.

Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic vaccines and the potential prevention of noncervical cancers in both men and women.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Steven A. Rosenberg, M.D.
National Cancer Institute (NCI)
BG 10-CRC RM 3-3940
10 CENTER DR
BETHESDA MD 20814
(301) 496-4164
sar@mail.nih.gov

Linda Williams, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 2B06
10 Center Drive
Bethesda, Maryland 20892
(866) 820-4505
linda_williams@nih.gov

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505
ncisbirc@mail.nih.gov

Clinical Trials Number:

NCT01585428

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