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Phase 1 trial of anti-CD19 chimeric antigen receptor T (CAR-T) cells with tumor necrosis alfa receptor superfamily 19 (TNFRSF19) transmembrane domain
- Source :
- Journal of Clinical Oncology. 37:2539-2539
- Publication Year :
- 2019
- Publisher :
- American Society of Clinical Oncology (ASCO), 2019.
-
Abstract
- 2539 Background: AntiCD19 CAR-T cells have shown encouraging anti-lymphoma activity. Decreasing the time from apheresis to CAR-T infusion can make this therapy available to pts with rapid progression. We present the interim results of a phase I clinical trial using on-site CAR-T manufacture. Methods: Adult pts with r/r CD19+ B cell lymphomas who failed ≥ 2 lines of therapy were enrolled. Autologous T cells were transduced with a lentiviral vector (Lentigen Technology, Inc,LTG1563) encoding an antiCD19 binding motif, CD8 linker and TNFRSF19 transmembrane region, and 4-lBB/CD3z domains. GMP-compliant manufacture was done using CliniMACS Prodigy, in a 12-day culture. Dose levels were 0.5, 1 and 2 x 106 CAR-T cells/kg. Lymphodepletion was done with cyclophosphamide (60mg/kg x 1) and fludarabine (25mg/m2/d x 3). Results: 7 pts (4 women, 3 men) were enrolled. Median age was 60y [range 43-69]. Diagnoses were DLBCL (n = 3) PMBCL, follicular lymphoma (FL), transformed FL, and transformed lymphoplasmacytic lymphoma; with a median of 4 previous treatments. Six pts had symptomatic refractory disease. CAR-T cell product manufacture was successful in all pts. Mean transduction rate was 44% [range 29-57]. CAR-T cell doses were 0.5 x 106/kg (n = 3) and 1 x 106/kg (n = 4). Median apheresis to infusion time was 13 days [range 13–20], 5 products were infused fresh. CAR-T persistence based on vector sequence, peaked in peripheral blood MNCs between days 14-21. Five pts are evaluable for safety. CRS grade 1 - 2 (Lee) occurred in 4 pts; with 3 requiring treatment. Grade 4 CRES (CARTOX-10) occurred in 1 pt, with resolution after corticosteroids; considered a DLT as it lasted more than 72 hours. No treatment-related mortality has occurred. 4/5 evaluable pts have achieved complete response. One pt did not respond and died. After a median follow up 3 months, all responding pts are alive and 1 relapsed 6 mo after treatment. Conclusions: Second generation antiCD19 CAR-T cells with TNFRS19 transmembrane domain have clinical activity against refractory NHL. Short manufacture time achieved by local CAR-T cell manufacture with the CliniMACS Prodigy enables treatment of a very high risk NHL population. Clinical trial information: NCT03434769.
- Subjects :
- Cancer Research
business.industry
Anti cd19
SUPERFAMILY
Chimeric antigen receptor
03 medical and health sciences
Transmembrane domain
0302 clinical medicine
Apheresis
Oncology
030220 oncology & carcinogenesis
Cancer research
Medicine
Tumor necrosis factor alpha
Car t cells
business
Receptor
030215 immunology
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi...........33b7ca422e02ac9dcf5e91fb76ae3d18
- Full Text :
- https://doi.org/10.1200/jco.2019.37.15_suppl.2539