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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Adaptimmune
Information provided by (Responsible Party):
Adaptimmune Identifier:
First received: May 2, 2011
Last updated: July 1, 2015
Last verified: July 2015
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 Intervention Phase
Biological: NY-ESO-1
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells Against Cancer-testis Antigens in Metastatic Melanoma

Resource links provided by NLM:

Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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:
  • Tumor Response [ Time Frame: Baseline, every 4 weeks until month 5 and then every other month through month 11 ] [ Designated as safety issue: No ]
    Clinical Activity of TCR gene therapy as assessed by RECIST (version 1.1) criteria and progression-free survival

  • 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 ] [ Designated as safety issue: No ]
    To determine the persistence of modified T cells in the peripheral blood and at tumor sites.

  • T cell function [ Time Frame: Weeks 4 and 8 post T cell infusion ] [ Designated as safety issue: No ]
    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.

Estimated Enrollment: 6
Study Start Date: May 2011
Estimated Study Completion Date: May 2031
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.
  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 identifier: NCT01350401

United States, Connecticut
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Harriet Kluger, MD    203-737-2572   
United States, Missouri
Washington University in St. Louis Recruiting
St. Louis, Missouri, United States, 63110
Contact: Gerald P Linette, MD, PhD    314-362-5677   
Sponsors and Collaborators
Principal Investigator: Gerald P Linette, MD, PhD Washington University School of Medicine
Principal Investigator: Harriet Kluger, MD Yale New Haven Hospital
  More Information

No publications provided

Responsible Party: Adaptimmune Identifier: NCT01350401     History of Changes
Other Study ID Numbers: ADP 01611
Study First Received: May 2, 2011
Last Updated: July 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas processed this record on November 27, 2015