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

This study has been terminated.
(Terminated due to withdrawal of support from our collaborator.)
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00704938
First received: June 24, 2008
Last updated: October 18, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Kidney Cancer
Melanoma (Skin)
Unspecified Adult Solid Tumor, Protocol Specific
Biological: aldesleukin
Biological: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes
Biological: autologous dendritic cell-adenovirus p53 vaccine
Biological: filgrastim
Drug: cyclophosphamide
Drug: fludarabine phosphate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Clinical Response (Complete Response + Partial Response) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
    Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse events module.


Enrollment: 3
Study Start Date: June 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC
Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
Biological: aldesleukin
Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.
Other Name: Proleukin
Biological: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes
Intravenous (IV) anti-p53 TCR transduced PBL will be administered at a a dose of 1 x 10^8 cells to 5 x 10^10 cells.
Biological: autologous dendritic cell-adenovirus p53 vaccine
Ad-p53 DC vaccine, up to 2 x 10^8 ad-p53 DCs per dose will be administered subcutaneously, divided into 4 injections, one into each of the 4 extremities. Ad-p53 DCs will be administered subcutaneously on day 7 (± 2 days), day 14 (between day 14 and day 18), and day 28 (between day 25 and day 42) post T cell infusion.
Biological: filgrastim
subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).
Other Name: growth colony stimulating factor (GCSF)
Drug: cyclophosphamide
60mg/kg/day (Days-7,-6)
Other Name: Cytoxan
Drug: fludarabine phosphate
25mg/m^2 (Days -5, -4, -3, -2, and -1)
Other Name: Fludara
Experimental: anti-p53 TCR PBL + DC + IL-2: Other histology
Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
Biological: aldesleukin
Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.
Other Name: Proleukin
Biological: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes
Intravenous (IV) anti-p53 TCR transduced PBL will be administered at a a dose of 1 x 10^8 cells to 5 x 10^10 cells.
Biological: autologous dendritic cell-adenovirus p53 vaccine
Ad-p53 DC vaccine, up to 2 x 10^8 ad-p53 DCs per dose will be administered subcutaneously, divided into 4 injections, one into each of the 4 extremities. Ad-p53 DCs will be administered subcutaneously on day 7 (± 2 days), day 14 (between day 14 and day 18), and day 28 (between day 25 and day 42) post T cell infusion.
Biological: filgrastim
subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).
Other Name: growth colony stimulating factor (GCSF)
Drug: cyclophosphamide
60mg/kg/day (Days-7,-6)
Other Name: Cytoxan
Drug: fludarabine phosphate
25mg/m^2 (Days -5, -4, -3, -2, and -1)
Other Name: Fludara

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 aldesleukin
    • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704938

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Responsible Party: Steven A. Rosenberg, NCI - Surgery Branch
ClinicalTrials.gov Identifier: NCT00704938     History of Changes
Other Study ID Numbers: 080155, NCI-08-C-0155, NCI-P07215
Study First Received: June 24, 2008
Results First Received: July 10, 2012
Last Updated: October 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
recurrent renal cell cancer
stage IV renal cell cancer
recurrent melanoma
stage IV melanoma
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Melanoma
Neoplasm Metastasis
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014