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Phase II Study in Metastatic Renal Cell Cancer Using Cultured, Tumor-Reactive Lymphocytes and Interleukin-2


Phase 1
18 Years
N/A
Not Enrolling
Both
Kidney Neoplasms

Thank you

Trial Information

Phase II Study in Metastatic Renal Cell Cancer Using Cultured, Tumor-Reactive Lymphocytes and Interleukin-2


Background:

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.

Objectives:

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.

Eligibility:

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.

Design:

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
regimen.

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.

Inclusion Criteria


- INCLUSION CRITERIA: CELL HARVEST:

- Patients must have metastatic renal cell cancer.

- age greater than or equal to 18 years.

- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at
entry to the trial.

- Life expectancy of greater than three months.

- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental
treatment being evaluated in this protocol depends on an intact immune system.
Patients who are human immunodeficiency virus (HIV) seropositive can have decreased
immune competence and can thus be less responsive to the experimental treatment and
more susceptible to it's toxicities.)

- Seronegative for hepatitis B antigen.

- Seropositive for Epstein-Barr Virus (EBV).

- Patients with electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia or
arrythmias or age greater than 50 years must have a normal stress cardiac test
(stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine
echocardiogram or other stress test).

- Patients who have a recent prolonged history of cigarette smoking or symptoms of
respiratory dysfunction must have pulmonary function testing with an forced
expiratory volume in 1 second (FEV(1)) greater than 60% predicted.

EXCLUSION CRITERIA: CELL HARVEST:

-Active systemic infections, coagulation disorders, contra-indications to receiving
interleukin-2 (IL-2) or major medical illnesses of the cardiovascular, respiratory or
immune system.

INCLUSION CRITERIA: CELL INFUSION:

- Patients must have measurable metastatic renal cell cancer and have tumor progression
after therapy with interleukin-2 (IL-2).

- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at
entry to the treatment phase of this trial.

- Platelet count greater than 100,000/mm^3.

- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three
times the upper limit of normal.

- Serum creatinine less than or equal to 1.6 mg/dl.

- Total bilirubin less than or equal to 1.6 mg/dl or direct bilirubin less than or
equal to 0.5 mg/dl.

- Life expectancy of greater than three months.

- At the time of T-cell transfer, the patient must have a T-cell population which has
met the attached Certificate of Analysis for tumor recognition and safety testing.

- Any patient receiving interleukin-2 (IL-2) must sign a durable power of attorney.

- Male and Female patients must be willing to practice contraception during the
treatment phase of this study..

- Patients with asymptomatic brain metastases may be considered eligible.

EXCLUSION CRITERIA: CELL INFUSION:

- Potentially effective therapy for renal cell cancer (RCC) within four weeks of the
time the patient receives T-cell transfer (with the exception of local irradiation to
non-evaluated sites).

- Requirement for steroid therapy.

- Active systemic infections, coagulation disorders, contra-indications to receiving
interleukin-2 (IL-2) or major medical illnesses or the cardiovascular, respiratory or
immune system.

- Pregnant patients and nursing mothers will be excluded because of the unknown effects
of this therapy on the fetus or nursing infant.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

No

Principal Investigator

James Yang, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health

Authority:

United States: Federal Government

Study ID:

040277

NCT ID:

NCT00091611

Start Date:

September 2004

Completion Date:

March 2008

Related Keywords:

  • Kidney Neoplasms
  • Clinical Response
  • Intravenous
  • Intra-Arterial
  • Lymphodepletion
  • Traffic of Cells
  • T-Cell Transfer
  • Renal Cell Carcinoma
  • Metastatic Renal Cell Cancer
  • Neoplasms
  • Carcinoma, Renal Cell
  • Kidney Neoplasms

Name

Location

National Cancer Institute (NCI)Bethesda, Maryland  20892