title: Strategy for a multicenter phase I clinical trial to evaluate globin gene transfer in beta-thalassemia.
abstract: Globin gene transfer in autologous hematopoietic stem cells offers a potentially curative treatment option for patients suffering from beta-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 beta-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.
authors: Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. m-sadelain@ski.mskcc.org
authors: Michel
authors: M
authors: Sadelain
authors: Isabelle
authors: I
authors: Rivière
authors: Xiuyan
authors: X
authors: Wang
authors: Farid
authors: F
authors: Boulad
authors: Susan
authors: S
authors: Prockop
authors: Patricia
authors: P
authors: Giardina
authors: Aurelio
authors: A
authors: Maggio
authors: Renzo
authors: R
authors: Galanello
authors: Franco
authors: F
authors: Locatelli
authors: Evangelia
authors: E
authors: Yannaki
mesh_terms: D000328:Adult; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D015337:Multicenter Studies as Topic; D019172:Transplantation Conditioning; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*