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Kidney CancerPhase 2NCT00704938

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

A Phase 2 study testing aldesleukin, anti-p53 T-cell receptor-transduced peripheral blood lymphocytes and autologous dendritic cell-adenovirus p53 vaccine in people with Kidney Cancer and Melanoma (Skin), run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
aldesleukin, anti-p53 T-cell receptor-transduced peripheral blood lymphocytes and autologous dendritic cell-adenovirus p53 vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Jun 2008to Aug 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

    Bethesda, Maryland, 20892-1182

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
aldesleukin, anti-p53 T-cell receptor-transduced peripheral blood lymphocytes, autologous dendritic cell-adenovirus p53 vaccine, filgrastim, cyclophosphamide
Keywords
recurrent renal cell cancer, stage IV renal cell cancer, recurrent melanoma, stage IV melanoma, unspecified adult solid tumor, protocol specific
Medical subject headings
Kidney Neoplasms, Melanoma, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • aldesleukinBiological

    Also called Proleukin

    Intravenous (IV) aldesleukin 720,000 IU/kg every 8 hours for a maximum of 15 doses.

  • anti-p53 T-cell receptor-transduced peripheral blood lymphocytesBiological

    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.

  • autologous dendritic cell-adenovirus p53 vaccineBiological

    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.

  • filgrastimBiological

    Also called growth colony stimulating factor (GCSF)

    subcutaneously at a dose of 5 mcg/kg/day (not to exceed 300 mcg/day).

  • cyclophosphamideDrug

    Also called Cytoxan

    60mg/kg/day (Days-7,-6)

  • fludarabine phosphateDrug

    Also called Fludara

    25mg/m^2 (Days -5, -4, -3, -2, and -1)

Study groups in NCT00704938
Study groupRoleWhat they receive
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCCExperimentalPatients 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)
Receives: 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
anti-p53 TCR PBL + DC + IL-2: Other histologyExperimentalPatients 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)
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical Response (Complete Response + Partial Response)

    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.

    Measured: 5 months

Secondary outcomes (1)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse events module.

    Measured: 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionAug 2009
  4. Study completionAug 2009

Why it stopped: Terminated due to withdrawal of support from our collaborator.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00704938
Sponsor's protocol ID
080155
Other IDs
NCI-08-C-0155, NCI-P07215
Status last verified
Sep 2015
First submitted
24 Jun 2008
Last updated
28 Oct 2015
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing aldesleukin, anti-p53 T-cell receptor-transduced peripheral blood lymphocytes and autologous dendritic cell-adenovirus p53 vaccine in people with Kidney Cancer and Melanoma (Skin), run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Response (Complete Response + Partial Response) (time frame: 5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00704938.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2015.

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