1. Evaluation of Tumor Vaccine Generation in a Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant (AutoHCT)Followed By Lenalidomide Maintenance for Multiple Myeloma (MM) with or without Vaccination with Dendritic Cell/ Myeloma Fusions (DC/MM fusion vaccine): Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1401
- Author
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Avigan, David E., Shah, Nina, Logan, Brent, Zhu, Jiaxi, Bisharat, Lina, Callander, Natalie S., Chodon, Thinle, Dhakal, Binod, Efebera, Yvonne A., Geller, Nancy, Hematti, Peiman, Herman, Michele, Lazarus, Hillard M., McKenna, David H., Nelson, Courtney, Nooka, Ajay, O'Brien, Kelly, O'Donnell, Lynn C., Rapoport, Aaron P., and Rosenblatt, Jacalyn
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CANCER vaccines , *MULTIPLE myeloma , *MANUFACTURED products , *VACCINE manufacturing , *PACLITAXEL , *VACCINES , *CLINICAL trials - Abstract
BMT CTN 1401 is an academically led randomized study of a personalized cancer vaccine in which the combination of DC/MM fusion vaccine and lenalidomide maintenance after autoHCT is compared with maintenance alone as upfront treatment of MM (NCT#02728102). Assessment of the percentage of patients achieving CR and therapy-induced changes in MM-specific immunity are the primary clinical and immunologic endpoints, respectively. The protocol represents a transformative open source approach to cell therapy in MM and required collection of tumor cells prior to treatment initiation and vaccine production at day 60 after autoHCT. The process featured a multi-step approach of procedural standardization, training, and centralized verification of manufactured product/release criteria. Here we present initial analysis of accrual and vaccine manufacturing. Enrollment of 203 patients completed within 26 months with 140 patients randomized. Drop-out rate from enrollment to randomization was 31% (expected 30%). Sixty-eight patients were randomized to the DC/MM fusion vaccine arm, with 63 having products successfully manufactured and approved for release at 14 manufacturing sites. Vaccine products for 5 patients were not approved for release for the following reasons: final TC/DC viability did not meet release criteria (n = 3), product failed to meet sterility release criteria (n = 1), and disease progression prior to manufacture (n = 1). Among 63 participants who received vaccine, mean DC viability and CD86 expression was 79.3% (Standard Deviation = 11.3) and 80.6% (SD = 12.9), respectively. Mean viability and percent cells co-expressing DC and tumor antigens was 78.6% (SD = 13.0) and 47.9% (SD = 11.4), respectively. The process devised for BMT CTN 1401 led to rapid patient accrual and successful point-of-care DC/MM fusion vaccine generation. Feasibility of serial sample collection and performance of immunologic correlates were demonstrated. This multi-center collaboration highlights the development of a personalized tumor vaccine platform that serves as a model for future immunotherapy trials in MM. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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