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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Cervical Cancer, Oropharyngeal Cancer, Vaginal Cancer, Anal Cancer, Penile Cancer

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Trial Information

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


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 human
papillomavirus-associated cancer.

- Prior platinum-based chemotherapy is required.

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 IV) on days -7 and -6 and fludarabine (25 mg/m2/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. 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.

Inclusion Criteria


-INCLUSION CRITERIA:

1. 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.

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

3. 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.

4. Greater than or equal to 18 years of age.

5. Able to understand and sign the Informed Consent Document

6. Clinical performance status of 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 receiving the preparative
regimen.

9. 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.

10. 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

11. 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.

12. 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:

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

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. Concurrent systemic steroid therapy.

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

6. History of coronary revascularization or ischemic symptoms.

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

8. 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.

9. Documented FEV1 less than or equal to 60% of predicted tested in patients with i) a
prolonged history of cigarette smoking or ii) symptoms of respiratory dysfunction.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the objective tumor response and duration

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Steven A Rosenberg, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

120116

NCT ID:

NCT01585428

Start Date:

April 2012

Completion Date:

April 2014

Related Keywords:

  • Cervical Cancer
  • Oropharyngeal Cancer
  • Vaginal Cancer
  • Anal Cancer
  • Penile Cancer
  • Immunotherapy
  • HPV-Associated Cancers
  • Cervical Cancer
  • Oropharyngeal Cancer
  • HPV Infection
  • Anus Neoplasms
  • Uterine Cervical Neoplasms
  • Vaginal Neoplasms
  • Oropharyngeal Neoplasms
  • Penile Neoplasms

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892