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Renal CancerPhase 1NCT00923390

Phase 1/2 Study of Metastatic Renal Cancer Using T-Cells Transduced With a T-Cell Receptor Which Recognizes TRAIL Bound to the DR4 Receptor

A Phase 1 study testing 2G-1 TCR Retroviral Vector-Transduced lyn, Aldesleukin and Cyclophosphamide in people with Renal Cancer and Kidney Cancer, run by National Cancer Institute (NCI) 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

Background: An experimental cancer treatment procedure involves taking a patient s own tumor or blood cells, modifying them with a gene that targets proteins on the surface of tumor cells, and growing those cells in a laboratory. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Renal Cancer, Kidney Cancer
What is being tested?
2G-1 TCR Retroviral Vector-Transduced lyn, Aldesleukin and Cyclophosphamide
How many people
5 participants
Where
1 siteUnited States
Study dates
2 Mar 2009to 24 Aug 2012
Phase
Phase 1
Are there results?
None posted in the registry

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Measurable metastatic clear cell renal cancer. Histologic diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
  • Patients must have previously received at least one systemic standard care regimens and have progressed or be found to be intolerant of standard therapies.
  • Greater than or equal to 18 years of age.
  • Willing to sign a durable power of attorney
  • Able to understand and sign the Informed Consent Document
  • Clinical performance status of ECOG 0 or 1.
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  • Life expectancy of greater than three months.
  • Patients of both genders must be willing to practice birth control during and for four months after receiving the preparative regimen.
  • Serology:
  • Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immunecompetence, and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
  • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  • Hematology:
  • Absolute neutrophil count greater than or equal to 1000/mm3 without the support of filgrastim.
  • WBC greater than or equal to 3000/mm3.
  • Platelet count greater than or equal to 100,000/mm3.
  • Hemoglobin greater than or equal to 8.0 g/dl.
  • Chemistry:
  • Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
  • Serum creatinine less than or equal to 1.6 mg/dl.
  • Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dl.
  • More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for alopecia or skin rash, which must have recovered to a grade 2 or less).
  • Patients who have previously received anti-CTLA4 antibody must have a normal colonoscopy with normal colonic biopsies.

Who cannot join

  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • Active systemic infections; coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
  • Concurrent systemic steroid therapy
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
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  • History of coronary revascularization or ischemic symptoms
  • Documented LVEF less than or equal to 45%. LVEF will be evaluated in patients with:
  • History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
  • Age greater than or equal to 60 years old
  • Documented FEV1 less than or equal to 60% predicted. Screening pulmonary function testing will be done in patients with:
  • A prolonged history of cigarette smoking (20 pk/year of smoking, who have not quit within the past 2 years).
  • Symptoms of respiratory dysfunction
  • Patients who have a history of more than two CNS metastases.
  • Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or shows significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

  • An experimental cancer treatment procedure involves taking a patient s own tumor or blood cells, modifying them with a gene that targets proteins on the surface of tumor cells, and growing those cells in a laboratory. The modified cells are then given back to the patient by intravenous (IV) transfusion, in the hope that the new cells will attack and destroy the cancer cells without harming healthy tissue.
  • This procedure has been used for melanoma patients, and researchers are now attempting to use this treatment for patients with renal (kidney) cancer. In the laboratory, this attack kills nearly all kidney cancers tested, but not normal tissues. However, the effectiveness and possible side effects of this treatment are still being studied.
Read more

Objectives:

  • To find out if cells modified to target DR4 and TRAIL (two proteins found on the surface of many kidney tumors) are effective in treating kidney cancer.
  • To determine the maximum tolerated dose (the highest dose that does not cause unacceptable side effects) of the modified cells.

Eligibility:

  • Patients 18 years of age and older with metastatic renal cancer whose disease has not responded to standard treatment.
  • Patients will be divided into two study branches: Arm A for those who will be receiving modified cells from their biopsied tumor, and Arm B for those who will be receiving their own modified white blood cells.

Design:

  • Five-stage treatment process, outpatient for stages 1 and 5 and inpatient for stages 2 through 4:
  • Work-up (1 to 2 weeks): Physical examination, heart and lung function tests, imaging tests, blood and/or tumor samples taken.
  • IV chemotherapy (1 week): Cyclophosphamide and fludarabine to prepare for the new cell infusion.
  • IV cell infusion and treatment with IL-2 to support the modified cells (4 days).
  • Recovery (1 to 2 weeks): Recover from effects of chemotherapy and infusion.
  • Follow-up (every 1 to 6 months): Return to clinic for physical exam, review of side effects, other tests.
  • Follow-up evaluations will continue to determine the success of the treatment.
  • Evaluations during the treatment period:
  • Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
  • Blood and urine tests.
  • Disease evaluation and monitoring on both inpatient and outpatient basis.
  • Because researchers do not know the long-term side effects of gene therapy, patients will be asked to participate in long-term follow up for up to 15 years. The follow-up will involve yearly physical exams and medical history, and blood collection (3, 6 and 12 months after treatment, and every year after that).
Read the detailed description

Background:

  • The clinical administration of tumor-reactive T-cells grown in vitro is a highly active therapy for patients with metastatic melanoma in experimental protocols when they are combined with preparative lymphodepleting chemotherapy and systemic IL-2.
  • We cloned a novel T-cell from the blood of a patient with renal cell cancer (RCC), which recognizes nearly all human renal cancer lines irrespective of MHC haplotype.
  • The alpha sign and beta sign chain of T-cell receptor from this clone, 2G-1, can be introduced into human lymphocytes by retroviral transduction and confers this same recognition of RCC.
  • This TCR was found to recognize TNF-related apoptosis inducing ligand (TRAIL) bound to its receptor DR4.
  • Both TRAIL and agonist antibodies to DR4 have tumor specificity and are in current clinical trials for cancer.
  • Two amino acid modifications of the native TCR greatly augmented its recognition of RCCs without altering background reactivity.

Objectives:

  • Primary:
  • Determine if the administration of T-cells retrovirally transduced with the 2G-1 TCR, with preparative chemotherapy and IL-2, can cause the regression of metastatic RCC.
  • To identify the maximum tolerated dose (MTD) for cells incorporating a TCR in PBL and in TIL.
  • Secondary:
  • Determine the toxicities of these T-cells administered in the above fashion.
  • Determine TCR and vector presence in the post treatment phase.

Eligibility:

  • Patients with measurable metastatic clear cell renal cancer who have previously received at least one systemic standard care regimen and have progressed or be found to be intolerant of standard therapies.
  • Patients must be eligible for high-dose IL-2.
  • Patients must not have active or clinically symptomatic CNS metastases within the previous 3 months.
  • Patients must have acceptable hematopoietic and major organ function as determined by laboratory and/or functional testing.

Design:

  • A phase I-II dose escalating protocol with 2 arms. Patients in Arm A will receive peripheral blood lymphocytes transduced with the 2G-1 TCR; patients in Arm B will receive renal TIL transduced with the 2G-1 TCR. Arm B will begin after a safe dose has been defined in Arm A.
  • Once MTD has been established for each arm, up to 24 patients will be enrolled in each arm of the phase II stage.
  • Patients will receive a nonmyeloablative but lymphocyte-depleting preparative regimen consisting of cyclophosphamide and fludarabine followed in one to four days by IV infusion of their transduced cells and subsequent IV aldesleukin administration.
  • Up to 106 patients may be enrolled over 3-4 years.
Being tested
2G-1 TCR Retroviral Vector-Transduced lyn, Aldesleukin, Cyclophosphamide, Fludarabine, (PG13-A(F/K-F-SGSG-T2a-B (opt) (2G-1 TCR) retroviral vector-transduced lymphocyte
Keywords
Renal Cancer, Immunotherapy, Clinical Response, Toxicity, Gene Therapy, Kidney Cancer
Medical subject headings
Kidney Neoplasms

What participants receive

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

What is being measured

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

  1. Determine if the administration of T-cells retrovirally transduced with the 2G-1 TCR, with preparative chemotherapy and IL-2, can cause the regression of metastatic RCC, and to identify the maximum tolerated dose for the 2G-1 TCr transduced cell...

Secondary outcomes (1)

  1. Determine the toxicities of these T-cells administered in the above fashion, and to determine TCR and vector presence in the post treatment phase.

Timeline

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

  1. First posted18 Jun 2009 (estimated)
  2. Study start2 Mar 2009
  3. Primary completion24 Aug 2012
  4. Study completion24 Aug 2012

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00923390
Sponsor's protocol ID
090092
Other IDs
09-C-0092
Status last verified
24 Aug 2012
First submitted
17 Jun 2009
Last updated
9 Apr 2019
Results posted
No

Publications

  • Motzer RJ, Michaelson MD, Rosenberg J, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Wilding G. Sunitinib efficacy against advanced renal cell carcinoma. J Urol. 2007 Nov;178(5):1883-7. doi: 10.1016/j.juro.2007.07.030. Epub 2007 Sep 17.

    PubMed 17868732

  • Bukowski RM, Kabbinavar FF, Figlin RA, Flaherty K, Srinivas S, Vaishampayan U, Drabkin HA, Dutcher J, Ryba S, Xia Q, Scappaticci FA, McDermott D. Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer. J Clin Oncol. 2007 Oct 10;25(29):4536-41. doi: 10.1200/JCO.2007.11.5154. Epub 2007 Sep 17.

    PubMed 17876014

  • Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer. 2008 Jul 15;113(2):293-301. doi: 10.1002/cncr.23552.

    PubMed 18457330

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 2G-1 TCR Retroviral Vector-Transduced lyn, Aldesleukin and Cyclophosphamide in people with Renal Cancer and Kidney Cancer, run by National Cancer Institute (NCI) 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?

The sponsor lists 23 inclusion and 15 exclusion criteria. 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 9 Apr 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early. Results are not available in the source record.

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?

Determine if the administration of T-cells retrovirally transduced with the 2G-1 TCR, with preparative chemotherapy and IL-2, can cause the regression of metastatic RCC, and to identify the maximum tolerated dose for the 2G-1 TCr transduced cell.... 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 NCT00923390, which also lists 3 linked publications.

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 9 Apr 2019.

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