Metastatic Melanoma Clinical Trial
Official title:
A Pilot Study of the Administration of Young Tumor Infiltrating Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
Background:
- 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 with aldesleukin (IL-2) a drug that keeps the
white blood cells active. These cells are called Tumor Infiltrating Lymphocytes, or TIL
and we have given this type of treatment to over 200 patients with melanoma.
- This study will use chemotherapy to prepare the immune system before this white blood
cell treatment. Our prior studies indicate that aldesleukin may not be required for
cell transfer.
Objectives:
- To see if chemotherapy and white blood cell therapy without aldesleukin is a safe and
effective treatment for metastatic melanoma.
Eligibility:
- Individuals at least 18 years of age and less than or equal to 70 years of age with
metastatic melanoma.
Design:
- Work up stage: Patients will be seen as an outpatient at the 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:
- Tumor Infiltrating Lymphocytes (TIL) can mediate the regression of bulky metastatic
melanoma when administered to the autologous patient along with high-dose aldesleukin
(IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen.
- IL-2 administration has been shown to increase the number of T regulatory cells and in
our trials we have found a direct relationship between the number of IL-2 doses and the
reconstitution of patients at one week with CD4+ Foxp3+ T regulatory cells.
- In our analysis of factors that relate to the ability of this treatment to mediate
objective responses, we have found a highly significant inverse correlation between
reconstitution of CD4+ Foxp3+ T regulatory cells and the likelihood of achieving an
objective response.
- In our prior clinical trials of cell transfer using TIL after lymphodepletion with or
without
2Gy total body irradiation, patients who experienced an objective response received
fewer doses of IL-2 compared to non-responders (p=0.007 and 0.03 respectively).
- High levels of the homeostatic T cell growth factor, IL-15, are present in patient
serum after the lymphodepleting regimen at the time of cell transfer.
- These factors raise the possibility that IL-2 administration is not required after cell
transfer.
OBJECTIVES:
- The primary objective of this trial is to determine whether objective responses can be
mediated in patients with metastatic melanoma who have received a lymphodepleting
chemotherapy regimen and adoptive transfer of young tumor infiltrating lymphocytes and
no IL-2 administration.
- The secondary objective involves the determination of the level of transferred cells in
the blood that persist at about 1 week and 1 month after transfer.
ELIGIBILITY:
- Patients greater than or equal to 18 years old with pathologically confirmed diagnosis
of metastatic melanoma.
- Patients with measurable disease, absolute neutrophil count greater than 1000/mm(3) and
platelet count greater than 100,000/mm(3).
- Patients not eligible to receive IL-2.
DESIGN:
- Patients with metastatic melanoma will undergo resection to obtain tumor for generation
of autologous TIL cultures.
- Patients will receive a non-myeloablative lymphodepleting preparative regimen
consisting of cyclophosphamide and fludarabine followed by the administration of young
autologous TIL.
- Patients will be evaluated for objective clinical response and for persistence of the
transferred cells.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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