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Phase II Study of Metastatic Cancer That Overexpresses p53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes and Dendritic Cell Vaccination

Phase 2
18 Years
Not Enrolling
Kidney Cancer, Melanoma (Skin), Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase II Study of Metastatic Cancer That Overexpresses p53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes and Dendritic Cell Vaccination



- Determine if the administration of anti-p53 T-cell receptor (TCR) gene-engineered
peripheral blood lymphocytes, high-dose aldesleukin, and adenovirus p53 dendritic cell
(DC) vaccine after a nonmyeloablative, but lymphoid-depleting, preparative regimen will
result in clinical tumor regression in patients with metastatic cancer that
overexpresses p53.


- Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.

- Determine the ability of a dendritic cell (DC) vaccine to restimulate TCR
gene-engineered cells in vivo.

- Determine the toxicity profile of this treatment regimen.

OUTLINE: Patients are stratified according to type of metastatic cancer (melanoma or renal
cell cancer vs all other cancers).

- Peripheral blood mononuclear cell (PBMC) collection: Patients undergo PBMC collection
via leukapheresis for the generation of the adenovirus p53 dendritic cell vaccine as
well as anti-p53 T-cell receptor (TCR) gene-engineered peripheral blood lymphocytes.

- Nonmyeloablative lymphocyte-depleting preparative regimen: Patients receive
cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine
phosphate IV over 30 minutes on days -5 to -1.

- Peripheral blood lymphocyte infusion: Patients receive anti-p53 TCR gene-engineered
peripheral blood lymphocytes IV over 20-30 minutes on day 0. Patients receive
filgrastim (growth colony stimulating factor (G-CSF)) subcutaneously (SC) once daily
beginning on day 1 or 2 and continuing until blood counts recover.

- High-dose aldesleukin: Patients receive high-dose aldesleukin IV over 15 minutes three
times daily on days 0-4 for up to 15 doses.

- Dendritic cell vaccine: Patients receive adenovirus p53 dendritic cell vaccine SC on
days 0, 7, 14, and 28.

Patients may receive one re-treatment course as above (nonmyeloablative preparative regimen,
peripheral blood lymphocyte infusion, high-dose aldesleukin, and dendritic cell
vaccinations) beginning 6-8 weeks after the last dose of high-dose aldesleukin.

After completion of study treatment, patients are followed periodically for up to 15 years.

Inclusion Criteria


- Diagnosis of metastatic cancer

- Tumor overexpresses p53 as assessed by immunohistochemistry (i.e., ≥ 5% tumor cells
stain positive for p53)

- Biopsy must be available to evaluate p53 expression

- Human leukocyte antigens 0201 (HLA-A*0201) positive

- Progressive or recurrent disease after prior standard therapy for metastatic disease

- Patients with melanoma or renal cell cancer must have previously received

- Patients with other histologies, not including hematologic malignancies, must
have previously received first-line and second-line or higher systemic standard
therapy (or effective salvage chemotherapy regimens)


- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Life expectancy > 3 months

- Absolute neutrophil count > 1,000/mm^3

- White blood cell (WBC) > 3,000/mm^3

- Platelet count > 100,000/mm^3

- Hemoglobin > 8.0 g/dL

- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 times
upper limit of normal

- Serum creatinine ≤ 1.6 mg/dL

- Total bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL in patients with Gilbert's syndrome)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 4 months after
completion of study treatment

- Patients who have previously received ipilimumab or ticilimumab must have a normal
colonoscopy with normal colonic biopsies

- Human immunodeficiency virus (HIV) antibody negative

- Hepatitis B antigen and hepatitis C antibody negative (unless antigen negative)

- No primary immunodeficiency (e.g., severe combined immunodeficiency disease)

- No active systemic infections

- No history of severe immediate hypersensitivity reaction to any of the agents used in
this study

- No coagulation disorders

- No myocardial infarction or cardiac arrhythmias

- No history of coronary revascularization

- No obstructive or restrictive pulmonary disease

- No contraindications for high-dose aldesleukin administration

- Left ventricular ejection fraction (LVEF) ≥ 45% in patients meeting any of the
following criteria:

- History of ischemic heart disease,

- chest pain,

- or clinically significant atrial and/or ventricular arrhythmias including, but
not limited to, atrial fibrillation,

- ventricular tachycardia,

- or second- or third-degree heart block

- At least 60 years of age

- Forced expiratory volume 1 (FEV_1) > 60% predicted in patients meeting any of the
following criteria:

- Prolonged history of cigarette smoking (> 20 pack/year within the past 2 years)

- Symptoms of respiratory dysfunction

- No other major medical illness of the cardiovascular,

- respiratory,

- or immune system


- See Disease Characteristics

- Recovered from prior therapy

- More than 4 weeks since prior and no concurrent systemic steroid therapy

- More than 4 weeks since other prior systemic therapy

- More than 6 weeks since prior ipilimumab

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical Response (Complete Response + Partial Response)

Outcome Description:

Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all lesions. Partial response is a 30% decrease in the sum of the longest diameter (LD) of target lesions.

Outcome Time Frame:

5 months

Safety Issue:


Principal Investigator

Steven A. Rosenberg, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NCI - Surgery Branch


United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

August 2009

Related Keywords:

  • Kidney Cancer
  • Melanoma (Skin)
  • Unspecified Adult Solid Tumor, Protocol Specific
  • recurrent renal cell cancer
  • stage IV renal cell cancer
  • recurrent melanoma
  • stage IV melanoma
  • unspecified adult solid tumor, protocol specific
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Melanoma
  • Neoplasm Metastasis



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182