Genetically Engineered PBMC and PBSC Expressing NY-ESO-1 TCR After a Myeloablative Conditioning Regimen to Treat Patients With Advanced Cancer (NYESO SCT)
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|ClinicalTrials.gov Identifier: NCT03240861|
Recruitment Status : Recruiting
First Posted : August 7, 2017
Last Update Posted : November 7, 2017
|Condition or disease||Intervention/treatment||Phase|
|HLA-A*0201 Positive Cells Present Locally Advanced Malignant Neoplasm NY-ESO-1 Positive Unresectable Malignant Neoplasm||Other: 18F-FHBG Biological: Aldesleukin Drug: Busulfan Biological: Cellular Therapy Procedure: Computed Tomography Biological: Filgrastim Drug: Fludarabine Procedure: Leukapheresis Drug: Plerixafor Procedure: Positron Emission Tomography||Phase 1|
I. To determine the safety of administering the combination of autologous peripheral blood mononuclear cells (PBMC) and CD34+ peripheral blood stem cells (PBSC) following a reduced intensity conditioning regimen, both of which have been genetically modified to express NY-ESO-1 TCR.
I. To determine the feasibility of delivering the combination of TCR transduced autologous PBMC and CD34+ PBSC to patients.
II. To determine the persistence of NY-ESO-1 TCR transduced PBMC and the progeny of TCR transduced PBSC in serial peripheral blood samples.
III. Objective response rate (ORR).
I. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer 9-4-[18F]fluoro-3-(hydroxymethyl)butylguanine ([18F]FHBG) with the goal of determining whether the adoptively transferred NY-ESO-1 TCR transduced PBSC home to bone marrow, differentiate into T cells and expand in secondary lymphoid organs and tumor deposits.
G-CSF AND PLERIXAFOR MOBILIZED LEUKAPHERESIS: Between 6 months and 3 weeks before infusion of cells, patients undergo G-CSF and plerixafor mobilization of CD34+ peripheral blood stem cells. Patients receive G-CSF subcutaneously (SC) on mobilization days 1-8 and plerixafor SC on mobilization days 4-7, during mobilization, patients will undergo mobilized leukapheresis to obtain PBSC. Patients also undergo an unmobilized leukapheresis on day -5 before infusion of cells in order to obtain PBMC.
CHEMOTHERAPY CONDITIONING REGIMEN: Patients receive busulfan intravenously (IV) on days -4 to -2 and fludarabine IV over 30 minutes on days -3 to -2.
Patients receive LV-NYESO TCR/sr39TK PBSC IV on day 0, and after approximately 24 hours, patients receive RV-NYESO TCR PBMC IV on day 1. Beginning on day 2, patients receive aldesleukin (interleukin-2 (IL) or IL-2) SC twice daily (BID) for up to 7 days. Patients undergo blood collection for safety and immune monitoring on days 0, 1, 3, 5, 7, 14, 30, 60, 90, and 120. Patients receive the PET tracer 18F-FHBG IV, and after 1 hour, undergo PET/computed tomography (CT) on days 25 and 120.
After completion of study treatment, patients are followed up every 2-3 months for 2 years, every 6 months for 5 years, and annually for 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 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) and Peripheral Blood Stem Cells (PBSC) After a Myeloablative Conditioning Regimen, With Administration of Interleukin-2, in Patients With Advanced Malignancies|
|Actual Study Start Date :||July 26, 2017|
|Estimated Primary Completion Date :||September 1, 2021|
|Estimated Study Completion Date :||September 1, 2022|
Experimental: Treatment (Genetically engineered PBMC and PBSC)
G-CSF AND PLERIXAFOR MOBILIZED LEUKAPHERESIS: Between 6 months and 3 weeks before infusion of cells, patients undergo G-CSF and plerixafor mobilization of CD34+ peripheral blood stem cells. Patients receive G-CSF SC on mobilization days 1-8 and plerixafor SC on mobilization days 4-7. Patients also undergo an unmobilized leukapheresis on day -5 before infusion of cells.
CHEMOTHERAPY CONDITIONING REGIMEN: Patients receive busulfan IV on days -4 to -2 and fludarabine IV over 30 minutes on days -3 to -2.
Patients receive LV-NYESO TCR/sr39TK PBSC IV on day 0, and after approximately 24 hours, patients receive RV-NYESO TCR PBMC IV on day 1. Beginning on day 2, patients receive aldesleukin SC BID for up to 7 days. Patients undergo blood collection for safety and immune monitoring on days 0, 1, 3, 5, 7, 14, 30, 60, 90, and 120. Patients receive 18F-FHBG IV, and after 1 hour, undergo PET/CT on days 25 and 120.
Other Name: Reporter Probe 18F-FHBG
Biological: Cellular Therapy
Given LV-NYESO TCR/sr39TK PBSC IV and RV-NYESO TCR PBMC IV
Other Name: Cell Therapy
Procedure: Computed Tomography
Other Name: Fluradosa
Procedure: Positron Emission Tomography
- Incidence of dose limiting toxicity [ Time Frame: Up to 90 days ]Safety will be assessed by monitoring and recording potential adverse effects of the treatment using the Common Toxicity Criteria at each study visit. Subjects will be monitored by medical histories, physical examinations and blood studies to detect potential toxicities from the treatment. If there are no dose limiting toxicities observed, the cohort will be expanded to 12 subjects. If 1/3 are observed, up to 6 subjects will be recruited. If less than 2/6 are observed, the cohort will be expanded to a total of 12 subjects. If a dose limiting toxicity is observed in 2 or more of 6 subjects, the
- Detection of replication competent retrovirus and replication competent lentivirus [ Time Frame: Up to 12 months post cell administration ]Will be assessed by polymerase chain reaction.
- Duration of overall complete response [ Time Frame: From the time measurement criteria has been first met for complete response until the first date that recurrent or progressive disease is objectively documented, assessed up to 15 years ]Will evaluate duration of overall complete response.
- Duration of overall response [ Time Frame: From the time measurement criteria is met for complete response/partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 15 years ]Will evaluate duration of overall response.
- Persistence of transduced T cells [ Time Frame: Time Frame: Up to 2 years after transgenic cell adoptive transfer ]
Analysis will be performed using immune monitoring techniques. The number of days until the percentage of cells expressing both NYESO-
1 TCR and CD3 drops below the baseline percentage.
- Engraftment and persistence of transduced progeny T cells [ Time Frame: Time Frame: Up to 2 years after transgenic cell adoptive transfer ]Analysis will be performed using immune monitoring techniques. The number of days until the vector copy number in the progeny T cells is undetectable.
- Engraftment and persistence of transduced T cells and progeny T cells [ Time Frame: Time Frame: Up to 2 years after transgenic cell adoptive transfer ]
Analysis will be performed both using immune monitoring and molecular techniques.
The number of days until the vector copy number in the T cells is undetectable.
- Feasibility of generation NY-ESO-1 TCR transgenic T cells and NY-ESO-1 TCR/sr39TK transgenic stem cells that meet the lot release criteria [ Time Frame: Time Frame: Up to 1 month after transgenic cell adoptive transfer ]
Feasibility of manufacturing will be assessed as:
The number of manufacturing products meeting the lot release criteria after an acceptable number of CD34+ cells have been obtained.
- Immunological monitoring will consist primarily of quantifying T cells bearing surface NY-ESO-1 TCR [ Time Frame: Up to 15 years ]Will be assessed by NY-ESO-1126-157/MHC (major histocompatibility complex) dextramer analysis. Functional assays like enzyme-linked immunosorbent assay, intracellular cytokine staining, and/or multicytokine array assays will complement the results. Immunological assays will be compared between 1) pre-infusion peripheral blood mononuclear cells and peripheral blood stem cells, 2) an aliquot of the engineered peripheral blood lymphocytes and stem cells at the time of infusion and 3) cells recovered from patients? peripheral blood after adoptive transfer.
- Objective response [ Time Frame: Up to 15 years ]Potential objective responses to this combinatorial immunotherapy will be recorded following Response Evaluation Criteria in Solid Tumors version 1.1 criteria.
- Persistence of TCR gene transduced cells [ Time Frame: Up to 15 years ]Will be assessed by semi quantitative deoxyribonucleic acid-polymerase chain reaction using primers specific for vector sequence.
- Time to disease progression [ Time Frame: Time from the date of cell infusion (day 0) to the date of progressive disease first documented, or death whichever occurs first, assessed up to 15 years ]Will evaluate length of time until disease progression.
- Regional uptake of 18F-FHBG within metastatic tumor sites and secondary lymphoid organs [ Time Frame: Up to 15 years ]Will be quantified by standardized uptake values normalized to the body weight of the patient. As an internal quality control, standardized uptake values will also be determined for several normal organs, such as muscle, liver and lungs. These measurements will allow us to identify technical problems in the standardized uptake value calculations, such as partially paravenous tracer administration. Findings from non-invasive positron emission tomography imaging will be compared with results from immune monitoring assays in blood samples at different intervals after NY-ESO-1 TCR cell transplant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03240861
|Contact: Antonio Ribas, M.D.||email@example.com|
|Contact: Siwen Hu-Lieskovan, M.D.||310-206-8477 ext firstname.lastname@example.org|
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Antoni Ribas 310-206-3928 email@example.com|
|Principal Investigator: Antoni Ribas|
|Principal Investigator:||Antoni Ribas, M.D.||UCLA / Jonsson Comprehensive Cancer Center|