Strategy for a multicenter phase i clinical trial to evaluate globin gene transfer in β-thalassemia

Michel Sadelain, Isabelle Rivière, Xiuyan Wang, Farid Boulad, Susan Prockop, Patricia Giardina, Aurelio Maggio, Renzo Galanello, Franco Locatelli, Evangelia Yannaki

Research output: Chapter in Book/Report/Conference proceedingConference contribution


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.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Number of pages7
Publication statusPublished - Aug 2010

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)00778923
ISSN (Electronic)17496632


  • cell therapy
  • globin gene regulation
  • lentiviral vector
  • non-myeloablative conditioning
  • stem cell engineering

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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