Gene and Vaccine Therapy in Treating Patients With Advanced Malignancies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01697527|
Recruitment Status : Recruiting
First Posted : October 2, 2012
Last Update Posted : September 13, 2017
|Condition or disease||Intervention/treatment||Phase|
|Malignant Neoplasm||Biological: aldesleukin Drug: fludarabine phosphate Drug: cyclophosphamide Other: laboratory biomarker analysis Biological: NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL Biological: dendritic cell vaccine therapy Radiation: fludeoxyglucose F 18 Procedure: positron emission tomography||Phase 2|
I. To evaluate whether we can safely administer NY-ESO-1 T cell receptor transduced autologous peripheral blood mononuclear cells (PBMCs) (up to 1x10^9 cells) along with an NY-ESO-1 dendritic cell vaccine and low dose IL-2 to patients with advanced malignancies.
II. To evaluate the feasibility of delivering two patient-specific cell therapies, the NY-ESO-1 TCR transgenic peripheral blood mononuclear cell (PBMC) and NY-ESO-1 (157-165) peptide pulsed dendritic cells (DC), within a technically challenging study design that requires other significant interventions, like a lymphodepleting conditioning regimen and post-infusion of subcutaneous low dose interleukin (IL)-2 (aldesleukin).
III. To determine the rate of objective tumor responses, by Response Evaluation Criteria in Solid Tumors (RECIST) objective response criteria.
I. To determine the persistence of NY-ESO-1 TCR-engineered cells. This will be determined by temporally analyzing peripheral blood samples for the presence of T cells with the transduced NY-ESO-1 TCR by tetramer or dextramer analysis.
II. To explore the homing and persistence of the adoptively transferred NY-ESO-1 TCR-engineered PBMC in secondary lymphoid organs and tumor deposits via positron emission tomography (PET)-based imaging using the PET tracer fluorodeoxyglucose ([18F]FDG).
CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 30 minutes on days -4 to -1.
TRANSPLANT: Patients receive NY-ESO-1 TCR transduced autologous PBMC IV on day 0. Patients also receive NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy intradermally (ID) on days 1, 14, and 30 and aldesleukin subcutaneously (SC) twice daily (BID) on days 1-14. Patients may receive 3 additional doses of NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy after day 90.
After completion of study treatment, patients are followed up at 30, 45, 60, and 75 days; every 3 months for 2 years; every 6 months for 3 years; and annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adoptive Transfer of NY-ESO-1 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) After a Nonmyeloablative Conditioning Regimen, With Administration of NY-ESO-1157-165 Pulsed Dendritic Cells and Interleukin-2, in Patients With Advanced Malignancies|
|Actual Study Start Date :||November 2, 2012|
|Estimated Primary Completion Date :||November 2, 2018|
|Estimated Study Completion Date :||November 2, 2019|
Experimental: Treatment (gene and vaccine therapy)
CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on days -5 to -4 and fludarabine phosphate IV over 30 minutes on days -4 to -1.
TRANSPLANT: Patients receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL IV on day 0. Patients also receive NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy ID on days 1, 14, and 30 and aldesleukin SC BID on days 1-14. Patients may receive 3 additional doses of NY-ESO-1 (157-165) peptide pulsed dendritic cell vaccine therapy after day 90.
Other Names:Drug: fludarabine phosphate
Other Names:Drug: cyclophosphamide
Other Names:Other: laboratory biomarker analysis
Correlative studiesBiological: NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL
Undergo NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL
Other Names:Biological: dendritic cell vaccine therapy
Given NY-ESO-1-157-165 peptide pulsed dendritic cell vaccine IDRadiation: fludeoxyglucose F 18
Undergo PET scan using [18F] FDG tracer
Other Names:Procedure: positron emission tomography
Undergo fludeoxyglucose F18 PET
- Clinical response [ Time Frame: Day +90 ]Will be determined by RECIST 1.1 Criteria on Day +90
- NY-ESO-1 TCR transgenic cell persistence, quantitated in PBMC samples [ Time Frame: Up to 6 years ]
- NY-ESO-1 TCR transgenic cell tumor trafficking [ Time Frame: Up to 40 days ]Regional uptake of fludeoxyglucose F18 within metastatic tumor sites and secondary lymphoid organs will be quantified by standardized uptake values (SUV) normalized to the body weight of the patient. The numbers of T lymphocytes will be quantified.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01697527
|United States, California|
|University of California at Los Angeles (UCLA )||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Arun Singh 310-829-5471 email@example.com|
|Principal Investigator: Arun Singh|
|Principal Investigator:||Arun Singh||Jonsson Comprehensive Cancer Center|