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Gene-Modified Lymphocytes, High-Dose Aldesleukin, and Vaccine Therapy in Treating Patients With Progressive or Recurrent Metastatic Cancer

Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Kidney Cancer; Melanoma (Skin); Unspecified Adult Solid Tumor, Protocol Specific

Intervention: aldesleukin (Biological); anti-p53 T-cell receptor-transduced peripheral blood lymphocytes (Biological); autologous dendritic cell-adenovirus p53 vaccine (Biological); filgrastim (Biological); cyclophosphamide (Drug); fludarabine phosphate (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: National Institutes of Health Clinical Center (CC)

Official(s) and/or principal investigator(s):
Steven A. Rosenberg, MD, PhD, Principal Investigator, Affiliation: NCI - Surgery Branch


RATIONALE: Gene-modified lymphocytes may stimulate the immune system in different ways and stop tumor cells from growing. High-dose aldesleukin may stimulate lymphocytes to kill tumor cells. Vaccines made from a gene modified virus and a person's dendritic cells may help the body build an effective immune response to kill tumor cells. Giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy works in treating patients with progressive or recurrent metastatic cancer.

Clinical Details

Official title: 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

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

Primary outcome: Clinical Response (Complete Response + Partial Response)

Secondary outcome: Number of Participants With Adverse Events

Detailed description: OBJECTIVES: Primary

- 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. Secondary

- 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.



- 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) PATIENT CHARACTERISTICS:

- 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

Locations and Contacts

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office, Bethesda, Maryland 20892-1182, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2008
Last updated: October 18, 2012

Page last updated: August 23, 2015

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