A Pilot Study of Genetically Engineered NY-ESO-1 Specific (c259) T Cells in HLA-A2+ Patients With Synovial Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Adaptimmune
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01343043
First received: April 26, 2011
Last updated: December 4, 2013
Last verified: December 2013
  Purpose

The purpose of this early (pilot) clinical trial is to test the effects (both good and bad) of chemotherapy and the NYESO T cells on patients with metastatic and recurrent synovial sarcoma.


Condition Intervention Phase
Synovial Sarcoma
Biological: NY-ESO-1 T Cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Genetically Engineered NY-ESO-1 Specific (c259) T Cells in HLA-A2+ Patients With Synovial Sarcoma

Resource links provided by NLM:


Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • Determine the response rate. [ Time Frame: Day 28, 60, 100, 180; Month 9, 12, then q6 months x 3 yrs ] [ Designated as safety issue: Yes ]
    To determine whether the administration of T cells genetically engineered to recognize a peptide derived from NY-ESO-1 in HLAA2+patients demonstrate a response rate consistent with that observed using similar NYESO-1 specific T cells plus aldesleukin in patients with synovial sarcoma.


Secondary Outcome Measures:
  • Evaluate persistence and expansion of NY-ESO-1 cells [ Time Frame: Daily Days 0-14, D21, D28, D42, D60, Mo: 3, 4, 5, 6, 9, 12; q6mo for 3 yrs ] [ Designated as safety issue: No ]
    Evaluate persistence and expansion of adoptively transferred NY-ESO-1 (c259) cells and correlate this with clinical responses; Monitor Tregs in the adoptively transferred cells and in patients treated, and compare clinical outcomes with Treg levels; and When possible, assess whether patients with progressive disease following NY-ESO-1 T cells experience a response following a second dose administered with aldesleukin.


Estimated Enrollment: 10
Study Start Date: March 2011
Estimated Study Completion Date: March 2029
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NY-ESO-1 T cell Infusion

NIH population: Subjects age between ages 4 to 35 will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.

CHOP population: Subjects age between ages 4 to 35 will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.

Biological: NY-ESO-1 T Cells
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0

Detailed Description:

Design

  • Patients will undergo apheresis at the enrolling institution. Fresh PBMC will be shipped to University of Pennsylvania and shipped back to the enrolling institution.
  • Patients will undergo lymphodepletion with denileukin diftitox, fludarabine and cyclophosphamide, then infusion of NY-ESO-1 genetically engineered T cells on Day 0.
  • Patients will be monitored for toxicity, antitumor effects and immune endpoints.
  • Patients with a PR or SD may receive a 2nd cycle no earlier than 60 days following completion of the first cycle if eligibility criteria are met. For patients with progressive disease, a 2nd cycle that includes high dose aldesleukin administered beginning on the day of T cell infusion may be administered no earlier than 60 days following completion of the first cycle if eligibility criteria are met.
  Eligibility

Ages Eligible for Study:   4 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Synovial sarcoma that has been treated with standard chemotherapy containing doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
  • Measurable disease
  • Synovial sarcoma and NY-ESO-1+ expression by immunohistochemistry
  • HLA-A2+
  • Age 4 to less than or equal to 55. NIH 4 to less or equal to 35. Washington University greater than or equal to 18.
  • Weigh more than 18 kg
  • All previous cytotoxic chemotherapy, monoclonal antibody therapy, immune, biologic or molecularly targeted therapy must be completed at least 3 weeks prior to study entry.
  • Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less
  • Performance Status. ECOG 0, 1 or 2 for age greater than 10 years. Lansky greater than or equal to 60 for children less than or equal to 10 years of age.
  • Life expectancy greater than 3 months
  • Left ventricular ejection fraction greater than or equal to 40% or fractional shortening greater than or equal to 28%
  • T.bilirubin < 2 mg/dl (Patients with Gilbert Syndrome exempt)
  • AST, ALT less than or equal to 2.5 x upper limit of normal
  • ANC > 750/mm3
  • Platelets > 75,000/mm3
  • Age-adjusted normal serum creatinine or a creatinine clearance greater than or equal to 60 ml/min/1.73m2
  • Ability to give informed consent for patients greater than 18 years of age. For patients less than 18 years of age the legal guardian must give informed consent.
  • Female and male patients (and when relevant their partners) must be willing to practice birth control (including abstinence) during and for two months after treatment.

Exclusion Criteria:

  • Clinically significant systemic illness that in the judgment of the PI would compromise the patient's ability to tolerate protocol therapy or significantly increase the risk of complications.
  • Untreated CNS metastasis
  • Previous treatment with genetically engineered NY-ESO-1 specific T cells. Previous vaccine therapy is not an exclusion criteria.
  • Lactating or pregnant females
  • Active HIV, HBV or HCV infection
  • Patients who require systemic corticosteroid or other immunosuppressive therapy. Immunosuppressive therapy must be stopped at least 14 days prior to cell infusion.
  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: NCT01343043

Contacts
Contact: Crystal Mackall, MD 301-402-5940 mackallc@mail.nih.gov
Contact: Melinda Merchant, MD 301-443-7955 melinda.merchant@mail.nih.gov

Locations
United States, Maryland
NIH Recruiting
Bethesda, Maryland, United States, 20852
Contact: Crystal Mackall, MD    301-402-5940    mackallc@mail.nih.gov   
Contact: Melinda Merchant, MD, PhD    301-443-7955    melinda.merchant@mail.nih.gov   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Christine Strait, BS    267-425-5837    straitc@email.chop.edu   
Principal Investigator: Stephan Grupp, MD, PhD         
Sponsors and Collaborators
Adaptimmune
Investigators
Principal Investigator: Crystal Mackall, MD National Institutes of Health (NIH)
Principal Investigator: Stephan Grupp, MD, PhD Children's Hospital of Philadelphia
  More Information

No publications provided

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01343043     History of Changes
Other Study ID Numbers: UPCC 04511
Study First Received: April 26, 2011
Last Updated: December 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Sarcoma

Additional relevant MeSH terms:
Sarcoma, Synovial
Sarcoma
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 22, 2014