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

Sponsor:	University of Pennsylvania
Collaborators:	Adaptimmune Ltd. National Cancer Institute (NCI)
Information provided by (Responsible Party):	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT01343043

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 carcinoma.

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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized 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:

MedlinePlus related topics: Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

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 ]
Disease Staging Evaluation: CT scan chest, head, abdomen, pelvis. MRI of tumro, FDG-PET, Bone Scan if indicated.

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 ]
Research Analysis

Estimated Enrollment:	10
Study Start Date:	March 2011
Estimated Study Completion Date:	March 2028
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: NIH Site Subjects age between ages 4 to 35 will receive one infusion of NY-ESO-1 genetically engineered T cells on Day 0	Other: NY-ESO-1 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

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

Sponsors and Collaborators

University of Pennsylvania

Adaptimmune Ltd.

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Crystal Mackall, MD

National Institutes of Health (NIH)

More Information

No publications provided

Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT01343043 History of Changes
Other Study ID Numbers:	UPCC 04511
Study First Received:	April 26, 2011
Last Updated:	January 10, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:

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 May 23, 2012