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



Status:Recruiting
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:4 - Any
Updated:10/3/2018
Start Date:September 27, 2012
End Date:May 31, 2020
Contact:US GSK Clinical Trials Call Center
Email:GSKClinicalSupportHD@gsk.com
Phone:877-379-3718

Use our guide to learn which trials are right for you!

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.

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.

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.
We found this trial at
6
sites
Tampa, Florida 33612
Phone: 877-379-3718
?
mi
from
Tampa, FL
Click here to add this to my saved trials
Bethesda, Maryland 20892
Phone: 877-379-3718
?
mi
from
Bethesda, MD
Click here to add this to my saved trials
Boston, Massachusetts 02115
Phone: 877-379-3718
?
mi
from
Boston, MA
Click here to add this to my saved trials
Houston, Texas 77030
Phone: 877-379-3718
?
mi
from
Houston, TX
Click here to add this to my saved trials
New York, New York 10032
Phone: 877-379-3718
?
mi
from
New York, NY
Click here to add this to my saved trials
Saint Louis, Missouri 63110
Phone: 877-379-3718
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials