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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 February 2017 by Adaptimmune
Sponsor:
Information provided by (Responsible Party):
Adaptimmune
ClinicalTrials.gov Identifier:
NCT01343043
First received: April 26, 2011
Last updated: February 22, 2017
Last verified: February 2017
  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
Intervention Model: Parallel Assignment
Masking: No masking
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 ]
    Evaluation of efficacy and duration of response of the treatment by assessment of Best Overall Response Rate according to RECIST v1.1

  • Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) in each cohort [ Time Frame: 1 Year ]
    Evaluation of efficacy and duration of response of the treatment by assessment of Overall Survival according to 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 ]
    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 ]
    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 ]
    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 ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1.


Estimated Enrollment: 65
Study Start Date: March 2011
Estimated Study Completion Date: March 2028
Estimated Primary Completion Date: October 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. (COMPLETE)
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 fludarabine. (COMPLETE)
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 4 treated with NY-ESO-1 T Cells
High NY-ESO-1 expression and the use of reduced dose cyclophosphamide plus fludarabine regimen.
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. PBMC will be shipped to a central manufacturer for gene transduction, activation and expansion, then cryopreserved and shipped back to the enrolling institution.
  • The trial seeks to enroll up to 65 patients, that is, up to 20 patients in Cohort 1 and up to 15 patients in Cohorts 2-4. Depending on the cohort patients are enrolled in, patients will undergo lymphodepletion with cyclophosphamide with or without fludarabine.

    • Cohort 1: Complete
    • Cohort 2: Up to 15 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide plus fludarabine on Days -3 and -2, and without fludarabine on Days -5 and -4.
    • Cohort 3: Up to 15 patients may be enrolled to achieve at least 10 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide only on Days -3 and -2. (Cohort Complete)
    • Cohort 4: Up to 15 patients may be enrolled to achieve at least 5 evaluable patients treated with NY-ESO-1ᶜ²⁵⁹T. Patients will undergo lymphodepletion with cyclophosphamide plus fludarabine on Days -7 to -5.

On Day 0, 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. Patients <40 kg will be dosed per body weight with a minimum 0.025x10⁹ transduced cells/kg, with a target dose of 0.125 x10⁹ 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 T cell infusion, provided eligibility criteria are met. The 2nd treatment cell infusion will be administered in the same manner as the first. Patients who meet the eligibility criteria may receive a 2nd infusion 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)
Sexes Eligible for Study:   All
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 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
    • Cohort 2 -Positive expression is defined as ≥1+ by immunohistochemistry in ≥1% cells, but not to exceed 2+ and/or 3+ in ≥ 50% of cells.
    • Cohort 3 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
    • Cohort 4 -Positive expression is defined as 2+ and/or 3+ by immunohistochemistry in ≥ 50% of cells.
  • HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 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 be completed at least 3 weeks prior to pre-infusion lymphodepletive chemotherapy.
  • 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 lymphodepletive chemotherapy.
  • ECOG 0-1, or for children ≤10 years of age, Lansky > 60
  • Life expectancy > 3 months
  • Left ventricular ejection fraction ≥ 40% or fractional shortening ≥ 28%
  • T. bilirubin < 2 mg/dl (Patients with Gilbert Syndrome total bilirubin <3xULN and direct bilirubin ≤ 35%)
  • AST, ALT ≤ 2.5 x upper limit of normal
  • ANC ≥ 1.0 x 10⁹/L
  • Platelets ≥ 75 x 10⁹/L
  • Age-adjusted normal serum creatinine or a creatinine clearance ≥ 40 ml/min
  • 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 4 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:

  • Active HIV, HBV, HCV or HTLV 1/2 infection (due to increased risk of complications during lymphodepleting 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.
  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: Sandra D'Angelo, MD 646-888-1394 lees4@mskcc.org

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Warren A Chow, MD, FACP    800-826-4673    wchow@coh.org   
Principal Investigator: Warren A Chow, MD, FACP         
United States, Florida
University of Miami, Sylvester Cancer Center Recruiting
Miami, Florida, United States, 33136
Principal Investigator: Breelyn Wilky, MD         
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: John Glod, MD    301-402-5940    john.glod@nih.gov   
Principal Investigator: John Glod, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Melissa Hohos, RN    617-582-7162    mhohos@partners.org   
Principal Investigator: George Demetri, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Principal Investigator: Brian Van Tine, MD, PhD         
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: Stephen Grupp, MD, PhD    267-425-5837    grupp@email.chop.edu   
Principal Investigator: Stephen Grupp, MD, PhD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Aaron S Reckeweg    713-794-4274    asreckew@mdanderson.org   
Contact: Nikki Weaver         
Principal Investigator: Dejka Araujo, MD         
Canada, Ontario
Princess Margaret Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Principal Investigator: Albiruni Razak, MB BCh         
France
Centre Léon Bérard & Université Claude Bernard Not yet recruiting
Lyon, France, 69373
Principal Investigator: Jean-Yves Blay, MD PhD         
Institut Gustave Roussy Not yet recruiting
Paris, France, 94800
Principal Investigator: Axel Lecesne, MD         
United Kingdom
University College London Hospital Not yet recruiting
London, United Kingdom, NW1 2PG
Principal Investigator: Sandra Strauss, PhD         
The Christie Hospital NHS Foundation Trust Not yet recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Fiona Thistlethwaite, MB BChir PhD MRCP         
Sponsors and Collaborators
Adaptimmune
Investigators
Study Chair: 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: February 22, 2017

Keywords provided by Adaptimmune:
Sarcoma
Cell Therapy
T Cell Therapy
NY-ESO-1
Immuno-oncology
Metastatic
Previously treated
T Cell Receptor

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 February 24, 2017