Redirected Auto T Cells for Advanced Myeloma
|ClinicalTrials.gov Identifier: NCT01352286|
Recruitment Status : Active, not recruiting
First Posted : May 11, 2011
Last Update Posted : October 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Genetic: Autologous Genetically modified T cells||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||March 2011|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||April 2031|
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.
- 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), ]
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 ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|
|Study Chair:||Aaron Rapoport, MD||University of Maryland Greenebaum Cancer Center|