A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for Human Papillomavirus-Associated Cancers
- 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.
- 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
- To study immunologic correlates associated with Young TIL therapy for HPV-associated
- To determine the toxicity of this treatment regimen.
- Patients greater than or equal to 18 years old with a pathologically confirmed
diagnosis of metastatic or locally advanced refractory/recurrent human
- Prior platinum-based chemotherapy is required.
- 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.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the objective tumor response and duration
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|