Redirected Auto T Cells for Advanced Myeloma
The purpose of this study is to 1) evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A2+ subjects and 2) measure the incidence of GVHD in patients following infusion of TCR modified autologous T cells.
Genetic: Autologous Genetically modified T cells
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/IIa, Dual-cohort, Two-site, Clinical Trial Evaluating the Safety and Activity of Redirected Autologous T Cells Expressing a High Affinity TCR Specific for NY-ESO-1 Administered Post ASCT in Patients With Advanced Myeloma|
- Frequency and severity of adverse events related to study treatment. [ Time Frame: Day -40 visit until relapse/progression or until 1 year, (whichever comes first), then during LTFU (years 1-15), ] [ Designated as safety issue: Yes ]
Occurrence of study related adverse events, defined as NCI CTC > grade 4 signs/symptoms, laboratory toxicities and clinical events that are probably or definitely related to investigational study treatment at any time from the infusion until 1 year. This will include infusional toxicity, and any toxicity probably or definitely related to the NY-ESO-1c259T including but not limited to:
- Neutropenia, thrombocytopenia, anemia, marrow aplasia
- Hepatic dysfunction
- Pulmonary infiltrates or other pulmonary toxicity
- Development of GVHD
NOTE: transplant-related toxicities, typically occurring within a month post-transplant, are excluded as investigational study-related adverse events.
Antitumor efficacy will be evaluated in depth through clinical, molecular and immunological secondary endpoints.
- Clinical Response Rate [ Time Frame: at day 180 ] [ Designated as safety issue: Yes ]Evaluate correlates of treatment efficacy by measuring (i) clinical response rates to treatment and (ii) the appearance of target antigen/MHC loss variants upon disease recurrence, as well as (iii) immunological parameters associated with product persistence, bioactivity and functionality.
|Study Start Date:||April 2011|
|Estimated Study Completion Date:||April 2031|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Experimental: Autologous Genetically modified T cells
Patients with advanced myeloma and who are candidates for autologous stem cell transplants, or syngeneic stem cell transplants (SSCT), will be eligible. Prior to full screening on this study, patients will undergo prescreening to evaluate HLA-A type and presence of NY-ESO-1c259T/LAGE antigen. Patients will undergo a steady-state mononuclear cell apheresis for T cell collection, with an optional second collection. Once mononuclear cells have been collected, patients (or donors in the case of SSCT) will then undergo hematopoietic stem cell mobilization. Patients will receive a dose >0.1-1 x 10¹º anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express high affinity NY-ESO-1c259 TCRs.
Genetic: Autologous Genetically modified T cells
Patients will undergo myeloma restaging at days +42, +100, 6 months, 9 months and 1 year post infusion. At this point, in accordance with FDA Guidelines, all patients will enter long term follow up (LTFU) and be followed biannually for monitoring for gene transfer delayed adverse events until year 5 post infusion. From year 5, all patients will require annual LTFU visits for monitoring for delayed adverse events until year 15 after receiving the genetically modified T cells.
Patients whose disease progresses prior to year 1 will enter LTFU at time of progression; however these patients will be seen quarterly from progression until year 1 post infusion and then follow the LTFU schedule mentioned above.
The primary objective of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target myeloma cells rather than their usual target. Study subjects must have systemic or multifocal myeloma requiring autologous stem cell transplantation whose disease has relapsed or incompletely responded to prior therapy or have high-risk features. Subjects must also have measureable disease on study entry, as defined by quantifiable or detectable levels of serum or urine paraprotein or elevated serum free light chains with an abnormal ratio.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01352286
|United States, Maryland|
|Greenebaum Cancer Center, University of Maryland|
|Baltimore, Maryland, United States, 21201|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Ed Stadtmauer, MD||Abramson Cancer Center of the University of Pennsylvania|
|Principal Investigator:||Aaron Rapoport, MD||University of Maryland Greenebaum Cancer Center|