A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers
- 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.
- 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.
- 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.
- 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.
Biological: Young TIL
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin for Human Papillomavirus-Associated Cancers|
- To determine the objective tumor response and duration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To determine the toxicity of this treatment regimen. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To study immunologic correlates [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
|Experimental: Group 1||
25 mg/m2/day for 5 daysDrug: Cycolphosphamide
60 mg/kg/day for 2 daysBiological: Young TIL
Between 1x10(9) to 2x10(11) TILBiological: Aldesleukin
720,000 IU/kg IV every eight hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
- 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 HPV-associated cancer.
- To study immunologic correlates associated with Young TIL therapy for HPV-associated cancers.
- 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 papillomavirus-associated cancer.
- 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 in two cohorts; patients iwth 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.
|Contact: Linda Williams, R.N.||(866) email@example.com|
|Contact: Steven A Rosenberg, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 email@example.com|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|