Phase I/II study of gene-modified WT1 TCR therapy in MDS & AML patient

• Research type

  Research Study

• Full title

  A single arm Phase I/II study of the safety and efficacy of gene-modified WT1 TCR therapy in patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) with low blast counts failing to achieve an IWG defined response following azacitidine therapy

• IRAS ID

  137028

• Contact name

  Emma Catherine Morris

• Contact email

  e.morris@ucl.ac.uk

• Eudract number

  2014-003111-10

• Duration of Study in the UK

  4 years, 0 months, 31 days

• Research summary

  This is a Phase I/II study to evaluate the safety and efficacy of the WT1 TCR therapy in patients with MDS or AML following azacitidine therapy. Myelodysplastic syndrome (MDS) is a chronic haematological disorder and the more severe forms of MDS are a precursor to acute myeloid leukaemia (AML). Azacitidine, a DNA hypomethylating agent, is now an established treatment strategy for more severe disease but Azacitidine is not curative and once patients no longer derive benefit, there is no established standard of care, and a median life expectancy of less than six months.
  Teams led by Prof. Emma Morris and Prof Hans Stauss from UCL developed a gene modified T cell receptor (TCR) which targets the WT1 antigen which is present at abnormally high levels on the surface of leukaemic and myelodysplastic cells. This generates T cells able to recognise WT1-expressing target cells which are infused back into the patient to initiate an immune response specific to leukaemic tissue. In this trial, participants (approx. 45 screened for 25 evaluable) with an HLA-A2 tissue type who have low blast count, stable MDS or AML but failed to reach an IWG response following Azacitidine therapy will be recruited. A leukapheresis sample will be taken and some of the patient’s own (autologous) T cells gene-modified using a GMP grade retroviral vector containing the genes for a WT1-specific, HLA-A2 restricted T cell receptor. Following cell manufacture, the patients will receive a preparative lymphodepletion regimen and then an infusion of their modified cells. Patients will also receive low dose IL-2 for 5 days post T cell infusion to further promote survival and proliferation of the infused T cells. Patient monitoring and follow-up for safety and efficacy of the infused cells will be carried out for at least 12 months.

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  14/LO/1644

• Date of REC Opinion

  31 Oct 2014

• REC opinion

  Further Information Favourable Opinion