CT Antigen TCR-Engineered T Cells for Myeloma
|Multiple Myeloma||Drug: Treatment with NY-ESO-1c259-modified T cells||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I/IIa, Open Label, Multiple Site Clinical Trial Evaluating the Safety and Activity of Engineered Autologous T Cells Expressing an Affinity-enhanced TCR Specific for NY-ESO-1 and LAGE-1 in Patients With Relapsed or Progressive Disease in Multiple Myeloma|
- Safety and Tolerability [ Time Frame: 3 Years ]Statistical analysis for this study will be primarily descriptive. The evaluable population includes any patient who has received the T cell infusion at the target dose range of ≥1e9-1e10 NY-ESO-1c259-T. For the primary safety endpoints, all adverse events will be described and exact 95% confidence intervals will be produced for adverse event rates, both overall and within major categories.
- Evaluate the direct anti-tumor activity of NY-ESO-1c259-T [ Time Frame: 180 days ]Analysis of secondary endpoints (e.g., response rate) will be descriptive and may include summary statistics such as means, median, standard deviations, range, and proportions. Confidence intervals will be computed. Endpoints that are taken repeatedly over time will be summarized and plotted against time since infusion to identify patterns over time.
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||April 2031|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Autologous genetically modified T cells
Patients with a confirmed diagnosis of myeloma, with measurable disease, and who have received prior therapy for their myeloma that includes an IMiDs and a proteasome inhibitor and who have relapsed or progressive disease, will receive treatment with NY-ESO-1c259-modified T cells. An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range.
Drug: Treatment with NY-ESO-1c259-modified T cells
An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to < 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range.
For patients whose disease progresses and whose tumor still expresses tumor antigen and HLA-A201, a second infusion of up to 5e10 cells may be given.
The primary objective of the study is to evaluate the safety and tolerability of autologous genetically modified T cells transduced to express the high affinity NY-ESO-1c259 TCR in HLA-A201 patients. Eligibility screening will be performed in two steps. First, patients will undergo prescreening to determine if they have the correct HLA type in order to respond to the engineered T cell therapy, and to test for presence of the target antigen, NY-ESO-1 and LAGE-1, in their tumor cells. Patients, who are HLA-A201 positive and test positive for expression of NY-ESO-1 and/or LAGE-1 in their myeloma tumor will move on to complete all screening procedures to determine eligibility for the study.
Patients will initially undergo a steady-state mononuclear cell apheresis for T cell collection. About 3-4 weeks later (to allow expansion/engineering/releasing the engineered T cells), patients will receive a short course of cytoreductive chemotherapy prior to receiving the engineered T cell infusion, comprised of 1.5 gm/m2 of cyclophosphamide, mesna will be given if in accordance with institutional standards.
At day 0, patients will receive a dose of ≥0.1-1 x 1010 anti-CD3/anti-CD28-costimulated autologous T cells which have been genetically modified to express affinity-enhanced NY-ESO-1 T cell receptors (TCRs). A minimum dose of 0.1≤x<1 x 109 will be permitted. Patients receiving this low dose level will be evaluated separately for safety and efficacy.
Patients will undergo myeloma restaging approximately 1 week prior to the T cell infusion, and post infusion at days +28, +42 (week 6), +100 and 6 months post infusion and then every 3 months until relapse/progression or until 1 year, whenever comes first. At this point, patients will be followed semi-annually for up to 5 years and then annually for long term follow-up for monitoring for delayed adverse events until 15 years after receiving the genetically modified T cells, in accordance with FDA Guidelines.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01892293
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|United States, Maryland|
|Greenebaum Cancer Center, University of Maryland|
|Baltimore, Maryland, United States, 21201|
|Study Chair:||Edward Stadtmauer, MD||University of Pennsylvania|