Phase II Study in Metastatic Renal Cell Cancer Using Cultured, Tumor-Reactive Lymphocytes and Interleukin-2
One area of therapeutic advancement in immunotherapy has been to identify autologous
tumor-reactive T-cells and expand them in vitro, and administer them in adoptive transfer
back to patients. These T-cells have been obtained either from tumor infiltrating
lymphocytes (TIL) which appear enriched for tumor-reactive T-cells or by in vitro
stimulation of peripheral blood T-cells from cancer patients. Recent success in patients
with melanoma has in large part been due to a T-cell expansion protocol described by Riddell
et al. using anti-CD3 (cluster of differentiation 3) and irradiated allogeneic feeder cells
and the use of conditioning chemotherapy prior to cell transfer. This current study uses the
results of these Surgery Branch adoptive cell therapy trials to study their potential in
patients with metastatic renal cell cancer.
The primary objective will be to determine whether adoptive lymphocyte transfer in
conjunction with preparative lympho-depletion chemotherapy and interleukin-2 (IL-2) may
result in clinical tumor regression in patients with metastatic renal cancer.
Patients with metastatic renal cell cancer who have failed conventional therapy with
interleukin-2, from whom tumor-reactive lymphocytes (from either peripheral blood, lymph
nodes or tumor-infiltrating lymphocytes) can be obtained and expanded in vitro.
Patients must meet specific safety laboratory criteria, be able to tolerate interleukin 2
(IL-2), and have no concurrent major medical illnesses or symptomatic brain metastases.
All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of
cyclophosphamide (60 mg/kg/day intravenous (IV)) on days -7 and -6 and fludarabine (25
mg/m^2/day intravenous (IV)) on days -5 through -1. On day 0 patients will receive an
infusion of their own tumor-reactive T cells grown in vitro (greater than or equal to 5x10^8
cells for a cycle) and then begin high-dose IL-2 (720,000 IU/kg intravenous (IV) every 8
hours for up to 15 doses).
Clinical and Immunologic response will be evaluated about 3 to 5 weeks after the treatment
This trial will be conducted as a phase II trial using a two-stage MinMax design which will
try to determine whether intravenous (IV) cell administration can produce a modest response
rate targeted to be greater than or equal to 35 % (p1=0.35) as opposed to an undesirably low
response rate of less than 15% (p0=0.15). If at least 3 patients of 15 have an objective
response (partial response (PR) or complete response (CR)) accrual will proceed to 28
patients, with a projected accrual over three years.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine whether Adoptive Lymphocyte Transfer in Conjunction with Preparative Lympho-depletion Chemotherapy and Interleukin-2 (IL-2) May result in Clinical Tumor Regression in Metastatic Renal Cancer
James Yang, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
|National Cancer Institute (NCI)||Bethesda, Maryland 20892|