Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers
| Status: | Completed |
|---|---|
| Conditions: | Colorectal Cancer, Cervical Cancer, Cervical Cancer, Cervical Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Women's Studies |
| Therapuetic Areas: | Oncology, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/17/2018 |
| Start Date: | April 13, 2012 |
| End Date: | August 1, 2016 |
A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for Human Papillomavirus-Associated Cancers
Background:
The human papillomavirus (HPV) can cause a number of cancers, including cervical and throat
cancers. The National Cancer Institute (NCI) Surgery Branch has developed an experimental
therapy that involves taking white blood cells from patients' tumors, growing them in the
laboratory in large numbers, and then giving the cells back to the patient. These cells are
called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to
over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people
with human papilloma virus (HPV)-related cancer. In this study, we are selecting a specific
subset of white blood cells from the tumor that we think are the most effective in fighting
tumors and will use only these cells in making the tumor fighting cells.
Objective:
The purpose of this study is to see if these specifically selected tumor fighting cells can
cause HPV-related cancers to shrink and to see if this treatment is safe.
Eligibility:
- Adults age 18-66 with HPV-related cancer who have a tumor that can be safely removed.
Design:
Work up stage: Patients will be seen as an outpatient at the National Institutes of Health
(NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab
tests, and other tests as needed.
Surgery: If the patients meet all of the requirements for the study they will undergo surgery
to remove a tumor that can be used to grow the TIL product.
Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells.
{Leukapheresis is a common procedure, which removes only the white blood cells from the
patient.}
Treatment: Once their cells have grown, the patients will be admitted to the hospital for the
conditioning chemotherapy, the TIL 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 will take up to 2 days.
The human papillomavirus (HPV) can cause a number of cancers, including cervical and throat
cancers. The National Cancer Institute (NCI) Surgery Branch has developed an experimental
therapy that involves taking white blood cells from patients' tumors, growing them in the
laboratory in large numbers, and then giving the cells back to the patient. These cells are
called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to
over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people
with human papilloma virus (HPV)-related cancer. In this study, we are selecting a specific
subset of white blood cells from the tumor that we think are the most effective in fighting
tumors and will use only these cells in making the tumor fighting cells.
Objective:
The purpose of this study is to see if these specifically selected tumor fighting cells can
cause HPV-related cancers to shrink and to see if this treatment is safe.
Eligibility:
- Adults age 18-66 with HPV-related cancer who have a tumor that can be safely removed.
Design:
Work up stage: Patients will be seen as an outpatient at the National Institutes of Health
(NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab
tests, and other tests as needed.
Surgery: If the patients meet all of the requirements for the study they will undergo surgery
to remove a tumor that can be used to grow the TIL product.
Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells.
{Leukapheresis is a common procedure, which removes only the white blood cells from the
patient.}
Treatment: Once their cells have grown, the patients will be admitted to the hospital for the
conditioning chemotherapy, the TIL 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 will take up to 2 days.
Background:
- Metastatic or locally advanced refractory/recurrent human papillomavirus
(HPV)-associated malignancies (cervical, vulvar, vaginal, penile, anal, and
oropharyngeal) are incurable and poorly palliated by standard therapies.
- Administration of autologous tumor infiltrating lymphocytes (TIL) generated from
resected metastatic melanoma can induce objective long-term tumor responses.
- Young TIL can be generated from HPV-associated tumors.
Objectives:
- To determine if autologous Young TIL infused in conjunction with high dose aldesleukin
following a non-myeloablative lymphodepleting preparative regimen can mediate tumor
regression in patients with metastatic or locally advanced refractory/recurrent
HPV-associated cancer.
- To study immunologic correlates associated with Young TIL therapy for HPV-associated
cancers.
- To determine the toxicity of this treatment regimen.
Eligibility:
- Patients greater than or equal to 18 years old with a pathologically confirmed diagnosis of
metastatic or locally advanced refractory/recurrent HIPV-16+ or HPV-18+ human
papillomavirus-associated cancer.
Design:
- Patients will undergo biopsy or resection to obtain tumor for generation of autologous
TIL cultures and autologous cancer cell lines.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide (60 mg/kg/day intravenous (IV)) on days -7 and -6 and fludarabine
(25 mg/m(2)/day IV) on days -5 through -1.
- On day 0 patients will receive between 1 times 10 (9) to 2 times 10(11) young TIL and
then begin high dose aldesleukin (720,000 IU/kg IV every 8 hours for up to 15 doses).
- Clinical and immunologic response will be evaluated about 4-6 weeks after TIL infusion.
- Initially, 18 evaluable patients will be enrolled in two cohorts; patients with cervical
cancer and those with non- cervical cancer. For each cohort, if 0 to 2 of the 18
patients experience a clinical response, then no further patients will be enrolled. If 3
or more of the first 18 evaluable patients enrolled have a clinical response, then
accrual will continue until a total of 35 evaluable patients have been enrolled in each
cohort. Up to 73 patients may be enrolled over approximately 3-4 years.
- Metastatic or locally advanced refractory/recurrent human papillomavirus
(HPV)-associated malignancies (cervical, vulvar, vaginal, penile, anal, and
oropharyngeal) are incurable and poorly palliated by standard therapies.
- Administration of autologous tumor infiltrating lymphocytes (TIL) generated from
resected metastatic melanoma can induce objective long-term tumor responses.
- Young TIL can be generated from HPV-associated tumors.
Objectives:
- To determine if autologous Young TIL infused in conjunction with high dose aldesleukin
following a non-myeloablative lymphodepleting preparative regimen can mediate tumor
regression in patients with metastatic or locally advanced refractory/recurrent
HPV-associated cancer.
- To study immunologic correlates associated with Young TIL therapy for HPV-associated
cancers.
- To determine the toxicity of this treatment regimen.
Eligibility:
- Patients greater than or equal to 18 years old with a pathologically confirmed diagnosis of
metastatic or locally advanced refractory/recurrent HIPV-16+ or HPV-18+ human
papillomavirus-associated cancer.
Design:
- Patients will undergo biopsy or resection to obtain tumor for generation of autologous
TIL cultures and autologous cancer cell lines.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide (60 mg/kg/day intravenous (IV)) on days -7 and -6 and fludarabine
(25 mg/m(2)/day IV) on days -5 through -1.
- On day 0 patients will receive between 1 times 10 (9) to 2 times 10(11) young TIL and
then begin high dose aldesleukin (720,000 IU/kg IV every 8 hours for up to 15 doses).
- Clinical and immunologic response will be evaluated about 4-6 weeks after TIL infusion.
- Initially, 18 evaluable patients will be enrolled in two cohorts; patients with cervical
cancer and those with non- cervical cancer. For each cohort, if 0 to 2 of the 18
patients experience a clinical response, then no further patients will be enrolled. If 3
or more of the first 18 evaluable patients enrolled have a clinical response, then
accrual will continue until a total of 35 evaluable patients have been enrolled in each
cohort. Up to 73 patients may be enrolled over approximately 3-4 years.
-INCLUSION CRITERIA:
1. Measurable metastatic or locally advanced refractory/recurrent malignancies that are
human papilloma virus 16 (HPV-16) or human papilloma virus 18 (HPV-18) high HPV
positive by in situ hybridization (ISH) or polymerase chain reaction (PCR) or any
cancer from the uterine cervix..
2. All patients must have received at least one standard chemotherapy or
chemoradiotherapy.
3. 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.
4. Greater than or equal to 18 years of age and less than or equal to age 70.
5. Able to understand and sign the Informed Consent Document
6. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
7. Life expectancy of greater than three months
8. 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.
9. Serology:
- Seronegative for human immunodeficiency virus (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 reverse transcription - polymerase chain reaction (RT-PCR)
and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
10. Women of child bearing potential must have a negative pregnancy test because of the
potentially dangerous effects of the treatment on the fetus.
11. Hematology
- Absolute neutrophil count greater than 1000/mm(3) without the support of
filgrastim
- White blood cell (WBC) greater than or equal to 3000/mm(3)
- Platelet count greater than or equal too 100,000/mm(3)
- Hemoglobin greater than 8.0 g/dl
12. Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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 that 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.
13. 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 or as specified in the
eligibility criteria in Section 2.1.1.
14. More than four weeks must have elapsed since any prior radiation therapy.
EXCLUSION CRITERIA:
1. 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.
2. 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
arrhythmias, obstructive or restrictive pulmonary disease.
3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
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 any of the agents used in
this study.
7. History of coronary revascularization or ischemic symptoms.
8. Any patient known to have an left ventricular ejection fraction (LVEF) less than or
equal to 45%.
9. 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.
10. Active Bleeding
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 866-820-4505
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