Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
- The 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 400 patients with melanoma.
- In this trial, we are determining if there is a difference in the response between patients who have received prior anti-PD1 treatment to those who have not received this prior ant-PD1 treatment.
- To determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not.
- Individuals at least 18 years and less than or equal to 70 years of age who have metastatic melanoma.
- Work up stage: Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
- Surgery: 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.
- Leukapheresis: Participants will have leukapheresis to collect additional white blood cells. (Leukapheresis is a common procedure which removes only the white blood cells from the patient.)
- Treatment: Participants will receive standard dose 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 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 take up to 2 days.
|Metastatic Melanoma||Drug: Aldesleukin Drug: Fludarabine Drug: Cyclophosphamide Biological: Young Tumor Infiltrating Lymphocytes (Young TIL) Drug: Keytruda (pembrolizumab) - ONLY FOR RETREATMENT||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Study for Metastatic Melanoma Using High Dose Chemotherapy Preparative Regimen Followed by Cell Transfer Therapy Using Tumor Infiltrating Lymphocytes Plus IL-2 With the Administration of Pembrolizumab in the Retreatment Arm|
- Determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not. [ Time Frame: Approximately 5 years ]
- Evaluate progression free and overall survival. [ Time Frame: Approximately 5 years ]
- Evaluate the safety and efficacy of pembrolizumab in combination with TIL therapy. [ Time Frame: Approximately 5 years ]
|Study Start Date:||November 19, 2013|
|Estimated Study Completion Date:||September 28, 2029|
|Estimated Primary Completion Date:||October 27, 2028 (Final data collection date for primary outcome measure)|
Patients will receive lymphocyte depleting chemotherapy (standard regimen) of cyclophosphamide and fludarabine followed by cells and high dose aldesleukin.(Patients in the RETREATMENT ARM will receive 4 doses of Pembrolizumab at the NIH Clinical Center.)
Administered at a dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15 minute period approximately every eight hours (+/- 1hr)beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 mlD5W with Mesna 15 mg/kg/day X 2 days over 1 hr.Biological: Young Tumor Infiltrating Lymphocytes (Young TIL)
Cells (young TIL) will be infused intravenously (i.v.) on the Patient Care Unti via non-filtered tubing, gently agitating the bag during infusion to prevent clumping.Drug: Keytruda (pembrolizumab) - ONLY FOR RETREATMENT
ONLY FOR RETREATMENT Patients who do not respond or who experience a partial or complete response and subsequently progress and have received prior therapy with either pembrolizumab or nivolumab may receive a second treatment. Patients in the RETREATMENT ARM will receive 4 doses of Pembrolizumab at the NIH Clinical Center as follows: -DAY 0 (two to four days after the last dose of fludarabine), Pembrolizumab 2mg/kg IV approximately 4 hours prior to cell infusion given over approximately 30 minutes; -DAY 21 (+/- 2 days) following cell infusion, Pembrolizumab 2mg/kg IV given over approximately 30 minutes; -DAY 42 (+/- 2 days)following cell infusion, Pembrolizumab 2mg/kg IV given over approximately 30 minutes; -DAY 63 (+/- 2 days) following cell infusion, Pembrolizumab 2mg/kg IV given over approximately 30 minutes
- Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
- In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gy or 12 Gy total body irradiation (TBI) objective response rates using RECIST criteria were 49%, 52%, and 72%, respectively. Of the 20 complete regressions seen in this trial, 19 are on-going at 70 to 114 months.
- The chemotherapy alone preparative regimen required in-patient treatment and was associated with significant neutropenia and thrombocytopenia requiring multiple transfusions and treatment for febrile neutropenia.
- With amendment D, to determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not; both groups will receive non-myeloablative lymphoid depleting preparative regimen followed by autologous young TIL and administration of high dose aldesleukin.
- To determine the toxicity of the treatment.
- Age greater than or equal to 18 and less than or equal to 70 years
- Evaluable metastatic melanoma
- Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL
- No contraindications to high-dose aldesleukin administration
- No concurrent major medical illnesses or any form of immunodeficiency
- Patients with metastatic melanoma will have lesions resected and after TIL growth is established, patients will receive ACT with TIL plus aldesleukin following high dose chemotherapy preparative regimen.
- Up to 64 patients may be enrolled over 4-5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01993719
|Contact: Colleen E Buckley, R.N.||(866) firstname.lastname@example.org|
|Contact: Steven A Rosenberg, M.D.||(866) email@example.com|
|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 firstname.lastname@example.org|
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|