UARK 2010-35, A Study of Expanded Natural Killer Cell Therapy for Multiple Myeloma (NK2010-35)
The purpose of this study is to determine the therapeutic efficacy of the exp-NK cell therapy in research participants with relapsed high risk MM [defined as gene expression profile (GEP) 70 gene score ≥0.66 and/or metaphase chromosomal abnormalities and/or high LDH ≥ 360U/L] by establishing the (near) complete response rate. Response rate will be compared to case matched historical controls (patients who relapsed on Total Therapy 2 or 3 with high-risk MM defined as above). Disease-free survival and overall survival will be captured but are not primary or secondary endpoints.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||UARK 2010-35, A Phase II Study of Expanded Natural Killer Cell Therapy for Multiple Myeloma|
- To determine the therapeutic efficacy of exp-NKcell therapy in research participants [ Time Frame: 2.5 Years ] [ Designated as safety issue: Yes ]Response rate will be compared to case matched historical controls (patients who relapsed on Total Therapy 2 or 3 with high-risk MM defined as above). Disease-free survival and overall survival will be captured but are not primary or secondary endpoints.
- The number of patients with adverse events, i.e. treatment related deaths, as a measure of safety. [ Time Frame: 3, 6, 9, 12 and 15 months ] [ Designated as safety issue: Yes ]If one treatment-related death occurs 3 patients will be enrolled. The trial will be halted if >2 treatment-related deaths occur in the first 6 patients. The trial will be halted if >3 treatment-related deaths occur in the first 9 patients. The trial will be halted if >4 treatment-related deaths occur in the first 12 patients. If ≤4 treatment related-deaths occur in the first 12 patients than a further 3 patients will be enrolled completing the enrollment of the first 15 patients.
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Velcade for Anti-MM therapy
Day(s) -9,-6,-2 3 doses of Bortezomib at 1.0 mg/m2, i.v.
bortezomib to be given days -9, -6, and -2 at 1.0mg/m2, i.v.
The use of auto-exp-NK cells in this protocol makes therapy available to all refractory high risk MM patients, 2/3 of whom would otherwise not have a suitable haploidentical donor. We have shown that NK cells can be expanded both from newly diagnosed high risk MM patients and from refractory, previously heavily treated patients, the very individuals in need of novel therapies such as exp-NK cell infusions. Furthermore, we observed that exp-NK cells have the ability to kill auto-MM cells in vitro compared to no killing with resting auto-NK cells. This may be due to the elevated activation state of exp-NK cells, which allows them to overcome otherwise dominant inhibitory signaling. The incorporation of the proteasome inhibitor bortezomib, which down regulates the principal NK cell inhibitory ligands on MM cells should further increase the efficacy of auto-exp-NK cells. Because there is no risk for GvHD, CD3+ T cell depletion will not be necessary for auto-exp-NK cell products.
|United States, Arkansas|
|University of Arkansas for Medical Sciences|
|Little Rock, Arkansas, United States, 72205|
|Principal Investigator:||Frits van Rhee, M.D., PHD.||University of Arkansas|