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Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01350401
Recruitment Status : Active, not recruiting
First Posted : May 9, 2011
Last Update Posted : October 24, 2017
Information provided by (Responsible Party):

Brief Summary:
The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health.

Condition or disease Intervention/treatment Phase
Melanoma Biological: NY-ESO-1 Phase 1 Phase 2

Detailed Description:
Purpose of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target melanoma cells rather than their usual target. Study subjects must have histologically or cytologically melanoma stage 3/4 and their tumor must express HLA Class 1 allele HLA-A*0201 for NY-ESO-1/LAGE. Subjects must also have measureable disease on study entry, as defined by at least one lesion that can be measured in at least one dimension >= 10mm with spiral CT scan.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma
Study Start Date : May 2011
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : May 2031

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: NY-ESO-1
Subject's tumor must express cancer testis antigen NYESO-1 and be HLA-A*02 positive
Biological: NY-ESO-1
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells

Primary Outcome Measures :
  1. NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3 [ Time Frame: Daily monitoring from Day1-Day 16, weekly thereafter through week 12, monthly thereafter through month 12. ]
    Determine the safety and tolerability of a fixed split-dose of autologous t cells transduced with lentiviral vector encoding an enhanced TCR after non-myeloablative chemotherapy.

Secondary Outcome Measures :
  1. Tumor Response [ Time Frame: Baseline, every 4 weeks until month 5 and then every other month through month 11 ]
    Clinical Activity of TCR gene therapy as assessed by RECIST (version 1.1) criteria and progression-free survival

  2. Persistence of modified T cells in the peripheral blood [ Time Frame: Days: 1, 5-9, 12-16, weekly thereafter through week 12, monthly thereafter through month 12, and during LTFU ]
    To determine the persistence of modified T cells in the peripheral blood and at tumor sites.

  3. T cell function [ Time Frame: Weeks 4 and 8 post T cell infusion ]
    To determine the functional properties and phenotype of modified T cells from peripheral blood and tumor sites. T cell function is essential to document the activity (or inactivity) of TCR positive T cells isolated from each patient at certain time points after adoptive transfer.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • Patients must have histologically or cytologically confirmed melanoma stage III/IV, unresectable
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan
  • One prior cytotoxic therapy for the treatment of metastatic disease is allowed. Unlimited regimens using biological agents (vaccines), immunotherapy, or targeted agents is permitted. For example, BRAF inhibitors and ipilimumab are permitted. Patients must have fully recovered from the acute toxicities related to any prior therapy. Prior therapy must be completed ≥28 days before the first dose of cyclophosphamide.
  • Age ≥18
  • Life expectancy of greater than 3 months
  • ECOG performance status ≤ 1

Patients must have normal organ and marrow function as defined below:

  • Leukocytes ≥ 3,000/mcL
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
  • Creatinine ≤ 2.0 mg/dl Or Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • The patient must express HLA class I allele HLA-A*0201 for NY-ESO-1/LAGE.
  • Patient must have proven positive tumor sample for NY-ESO-1 as determined by an H score for immunohistochemistry staining. Positive expression is defined as an H score ≥ 100 where the H score = [2 x (% cells 2+) + 3 x (% cells 3+)].

NOTE: The percentages of negative or weakly stained nuclei (i.e. 1+) are not to be included in the calculation of the H score.

  • Female subjects of childbearing potential must have a negative pregnancy test and both male and female (of childbearing potential) subjects must agree to use reliable methods of contraception during the study.
  • Ability of the patient (or legally authorized representative if applicable) to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • Patients who have had 2 or more regimens containing cytotoxic chemotherapy for metastatic melanoma.
  • Patients may not be receiving any other investigational agents.
  • Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study.
  • Active infection
  • Prior malignancy (except non-melanoma skin cancer) within 3 years.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. All patients will undergo a cardiac stress test for evaluation of cardiac function.
  • Pregnant or nursing females
  • Active infection with HIV, HBV or HCV as defined below, due to the immunosuppressive effects of cyclophosphamide used and the unknown risks associated with viral replication.
  • Positive serology for HIV
  • Active Hepatitis B infection as determined by test for hepatitis B surface antigen.
  • Active Hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV RNA by any RT-PCR or bDNA assay must be performed at screening by a local laboratory with a CLIA certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01350401

United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06520
United States, Missouri
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Principal Investigator: Gerald P Linette, MD, PhD Washington University School of Medicine
Principal Investigator: Harriet Kluger, MD Yale New Haven Hospital

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01350401     History of Changes
Other Study ID Numbers: ADP 01611
First Posted: May 9, 2011    Key Record Dates
Last Update Posted: October 24, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Adaptimmune:
Cell Therapy
T Cell Therapy
Previously treated
T Cell Receptor

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas