Strategy for a multicenter phase I clinical trial to evaluate globin gene transfer in β-thalassemia Conference Paper
| Authors: | Sadelain, M.; Riviere, I.; Wang, X.; Boulad, F.; Prockop, S.; Giardina, P.; Maggio, A.; Galanello, R.; Locatelli, F.; Yannaki, E. |
| Title: | Strategy for a multicenter phase I clinical trial to evaluate globin gene transfer in β-thalassemia |
| Conference Title: | 9th Cooley's Anemia Symposium |
| Abstract: | Globin gene transfer in autologous hematopoietic stem cells offers a potentially curative treatment option for patients suffering from β-thalassemia major who lack an HLA-matched hematopoietic stem cell donor. Based on extensive preclinical investigation, we are initiating a phase I clinical trial using G-CSF mobilized, autologous CD34+ cells transduced with a vector similar to the original TNS9 vector. Our first mobilizations in adult β-thalassemic subjects have been well tolerated and yielded the required CD34+ cell dose. To minimize toxicity to enrolled subjects, and in the absence of a demonstrated requirement for myeloablative conditioning, our trial will use a reduced intensity conditioning regimen. Because low vector titers may adversely affect efficacy and safety, we have focused on vector manufacturing processes. We are now in a position to transfer our globin lentiviral vectors in a clinically relevant dosage (averaging 0.8 vector copy per cell in bulk CD34+ cells) and to supply clinical grade vector to collaborating centers in the U.S.A. and in Europe. We anticipate that the first U.S. trial of globin gene transfer will start in 2010. © 2010 New York Academy of Sciences. |
| Keywords: | adult; busulfan; fludarabine; clinical trial; mortality; nonhuman; risk benefit analysis; conference paper; disease free survival; follow up; animals; mice; anemia; erythropoiesis; hemoglobin; allogenic bone marrow transplantation; age; gene transfer; genetic vectors; myeloablative conditioning; karnofsky performance status; peripheral blood stem cell; multicenter study; splenomegaly; gene therapy; lentivirus vector; beta thalassemia; blood transfusion; globin gene; graft versus host reaction; stem cell mobilization; beta-thalassemia; transplantation conditioning; cell therapy; erythrocyte; safety; phase 1 clinical trial; immunosuppressive treatment; clinical trials, phase i as topic; granulocyte colony stimulating factor; cd34 selection; autologous hematopoietic stem cell transplantation; multicenter studies as topic; gene transfer techniques; beta globin; globin gene regulation; lentiviral vector; non-myeloablative conditioning; stem cell engineering; ex vivo gene transfer; extramedullary hematopoiesis; iron overload |
| Journal Title | Annals of the New York Academy of Sciences |
| Volume: | 1202 |
| Conference Dates: | 2009 Oct 21-24 |
| Conference Location: | New York, NY |
| ISBN: | 0077-8923 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2010-08-01 |
| Start Page: | 52 |
| End Page: | 58 |
| Language: | English |
| DOI: | 10.1111/j.1749-6632.2010.05597.x |
| PUBMED: | 20712772 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: ANYAA" - "Source: Scopus" |
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