CT Antigen TCR-Engineered T Cells for Myeloma
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|ClinicalTrials.gov Identifier: NCT01892293|
Recruitment Status : Terminated (Sponsor Decision)
First Posted : July 4, 2013
Results First Posted : July 24, 2018
Last Update Posted : January 10, 2019
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Treatment with NY-ESO-1c259-modified T cells||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 15, 2013|
|Actual Primary Completion Date :||December 10, 2014|
|Actual Study Completion Date :||April 9, 2018|
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.
- Adverse Events Related to Study Treatment [ Time Frame: Up to 12 months ]Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3
- Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T [ Time Frame: 180 days ]Number of participants with response post-infusion as assessed by international uniform response criteria
- Peak Persistence of Modified T-cells in the Peripheral Blood [ Time Frame: Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter ]Measurement of NY-ESO-1ᶜ²⁵⁹T cells in blood (copies of WPRE per µg of genomic PBMC DNA)
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): 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|