A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma (NY-ESO-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Adaptimmune
Sponsor:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01343043
First received: April 26, 2011
Last updated: June 30, 2016
Last verified: June 2016
  Purpose
The purpose of this early (pilot) clinical trial is to test the effects (both good and bad) of chemotherapy and adoptive immunotherapy with T cells engineered to recognize NY-ESO-1 peptide in patients with unresectable, metastatic or recurrent synovial sarcoma.

Condition Intervention Phase
Synovial Sarcoma
Biological: NY-ESO-1(c259)T Cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Genetically Engineered NY-ESO-1 Specific NY-ESO-1ᶜ²⁵⁹T in HLA-A2+ Patients With Synovial Sarcoma

Resource links provided by NLM:


Further study details as provided by Adaptimmune:

Primary Outcome Measures:
  • Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to irRC and RECIST v1.1


Secondary Outcome Measures:
  • Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) [ Time Frame: From date of apheresis up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ] [ Designated as safety issue: Yes ]
    Determine if treatment with autologous genetically modified T cells, (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; and cardiac assessments, including ECG and ECHO/MUGA

  • Evaluation of the persistence of genetically modified T cells [ Time Frame: Day 0 up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ] [ Designated as safety issue: No ]
    Evaluation of the persistence of the infused T cells in the periphery

  • Percentage of total gene modified T cells with memory subtype [ Time Frame: Day 0 up to Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ] [ Designated as safety issue: No ]
    Memory phenotype of genetically modified T cells will be evaluated using flow cytometry.

  • After progressing and after receiving a 2nd dose of NY-ESO-1ᶜ²⁵⁹T, proportion of subjects with a confirmed Complete Response (CR) [ Time Frame: Month 3,6,9, Year 1, Every 3 months until 2 years, then Every 6 months until 5 years ] [ Designated as safety issue: No ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to irRC and RECIST v1.1.


Estimated Enrollment: 60
Study Start Date: March 2011
Estimated Study Completion Date: March 2028
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 treated with NY-ESO-1 T Cells
High NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine.
Biological: NY-ESO-1(c259)T Cells
Cytoreductive chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Experimental: Cohort 2 treated with NY-ESO-1 T Cells
Low NY-ESO-1 expression and the use of cyclophosphamide plus fludarabine.
Biological: NY-ESO-1(c259)T Cells
Cytoreductive chemotherapy followed by infusion with NY-ESO-1(c259) transduced autologous T cells. Subjects will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0.
Experimental: Cohort 3 treated with NY-ESO-1 T Cells
High NYESO-1 expression and the use of cyclophosphamide only for lymphodepletion rather than cyclophosphamide.
Biological: NY-ESO-1(c259)T Cells
Cytoreductive chemotherapy followed by infusion with NY-ESO-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 a central manufacturer for gene transduction, activation and expansion, then cryopreserved and shipped back to the enrolling institution.

  • Patients will undergo lymphodepletion with cyclophosphamide on Days -3 and -2 with or without fludarabine on Days -5 to -2. On Day 0, patients will receive a target dose of 5x10⁹/kg with a minimum of 1x10⁹/kg to a maximum of 6x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T.
  • The trial seeks to enroll up to 60 patients, that is up to 20 patients per cohort.
  • Cohort 1: Complete
  • Cohort 2: Up to 20 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T.
  • Cohort 3: Up to 20 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T.

Patients ≥40 kg will receive the minimum cell dose of at least 1x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T cells with a maximum of 6x10⁹ transduced cells. The target dose for this protocol is 5x10⁹ transduced NY-ESO-1ᶜ²⁵⁹T cells. For patients whose cell dose fails to meet the minimum cell dose requirement of 1x10⁹ transduced cells, those patients will still be eligible to receive NY-ESO-1ᶜ²⁵⁹T and participate on this protocol, however, an additional patient whose cell dose meets the minimum requirement of 1x10⁹ transduced cells will be added to the cohort.

  • Patients <40 kg will be dosed per body weight with a minimum 0.025x10⁹ transduced cells/kg, with a target dose of 0.125x10⁹ transduced cells/kg.
  • Patients will be monitored for toxicity, antitumor effects and immune endpoints.
  • Patients who have a confirmed response, or have stable disease for >3 months then progress may receive a 2nd cycle of treatment, provided eligibility criteria are met. The 2nd cycle of treatment will be administered in the same manner as the first treatment. Patients who meet the eligibility criteria may receive a 2nd treatment of NY-ESO-1ᶜ²⁵⁹T no sooner than 60 days and no later than 2 years following completion of the first treatment.
  Eligibility

Ages Eligible for Study:   4 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Synovial sarcoma that has been treated with standard chemotherapy containing ifosfamide and/or doxorubicin and remains: unresectable or metastatic or progressive/persistent or recurrent disease
  • Measurable disease
  • Patients must have proven positive tumor sample for NY-ESO-1 as follows:

    • Cohort 1 -Positive expression is defined as least ≥ 50% of cells that are 2+ and/or 3+ by immunohistochemistry.
    • Cohort 2 -Positive expression is defined as ≥1% of cells that are ≥1+ by immunohistochemistry, but not to exceed ≥ 50% of cells that are 2+ and/or 3+ by immunohistochemistry.
    • Cohort 3 -Positive expression is defined as at least ≥ 50% of cells that are 2+ and/or 3+ by immunohistochemistry.
  • HLA-A*0201, HLA-A*0205, and/or HLA-A*0206 by high resolution testing at a local or central laboratory
  • Weigh more than 18 kg
  • All previous cytotoxic chemotherapy, monoclonal antibody therapy, or immune therapy must be washed out 3 weeks before apheresis and must completed at least 3 weeks prior to study entry.
  • Systemic corticosteroid or other immunosuppressive therapy should be washed out 2 weeks before apheresis and must be completed at least 2 weeks prior to pre-infusion lymphodepletive chemotherapy.
  • Biologic or other approved molecular targeted small molecule inhibitors should be washed out 1 week or 5 half-lives (whichever is longer) before apheresis and must be completed at least 1 week or 5 half-lives (whichever is longer) prior to pre-infusion lymphodepletive chemotherapy.
  • Any grade 3 or 4 hematologic toxicity of any previous therapy must have resolved to grade 2 or less prior to apheresis and any grade 3 or 4 toxicity must have resolved to grade 2 or less prior to pre-infusion chemo
  • ECOG 0-1, or for children ≤10 years of age, Lansky ≥ 60
  • Life expectancy greater than 3 months
  • Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
  • T. bilirubin < 2 mg/dl (Patients with Gilbert Syndrome exempt)
  • AST, ALT ≤ 2.5 x upper limit of normal
  • ANC > 750/mm³
  • Platelets ≥ 75,000/mm³
  • Age-adjusted normal serum creatinine or a creatinine clearance ≥ 60 ml/min/1.73 m2
  • 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.
  • Male patients must be willing to practice birth control (including abstinence) during and for 2 months after treatment. Female patients must be willing to practice birth control (including abstinence) during treatment and for 4 months after gene modified cells are no longer detected in body.

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, HCV or HTLV 1/2 infection infection (due to increased risk of complications during the preparative regimen and confounding effects on the immune system). Active hepatitis B or C infection is defined by seropositive for hepatitis B surface antigen (HbSAg) or hepatitis C antibody with or without elevated liver transaminases.
  • 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, PhD 301-443-7955 melinda.merchant@mail.nih.gov

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Warren A Chow, MD, FACP    626-256-4673 ext 63494    WChow@coh.org   
Principal Investigator: Warren A Chow, MD, FACP         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Mihaela Druta, MD    813-745-3242    mihaela.druta@moffitt.org   
Principal Investigator: Mihaela Druta, MD         
United States, Maryland
National Cancer Institute 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, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sandra D'Angelo, MD    646-888-4159    dangelos@mskcc.org   
Principal Investigator: Sandra D'Angelo, MD         
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
Principal Investigator: Sandra D'Angelo, MD Memorial Sloan Kettering Cancer Center
  More Information

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT01343043     History of Changes
Other Study ID Numbers: ADP 04511 
Study First Received: April 26, 2011
Last Updated: June 30, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Adaptimmune:
Sarcoma

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

ClinicalTrials.gov processed this record on July 27, 2016