WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study

This trial concerns a novel approach to generating leukaemia antigen-specific T cells for adoptive cellular therapy in HLA-A*0201 patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML)

In this study, patient T cells will be gene-modified using a GMP grade retroviral vector containing the genes for a WT1-specific, HLA-A2-restricted T cell receptor. This ex vivo gene therapy will generate T cells expressing the WT1-specific TCR and thus able to recognise WT1-expressing target cells.

The autologous Cys1 WT1 TCR-transduced T cells will be re-infused back into adult leukaemia patients following lymphodepleting conditioning.

General Inclusion Criteria:

• Age ≥ 18 years and ≤ 75 years.
• Life expectancy ≥ 16 weeks (4 months).
• World Health Organisation (WHO) performance status of 0-2
• HLA A*0201 positive
• Completed previous course of chemotherapy ≥ 4 weeks prior to commencing the initial phase of the trial (leucapheresis for collection of patient PBMC).
• Peripheral blood total lymphocyte count > 0.5x109/L.
• Informed consent in writing and ability to co-operate with treatment and follow up.
• Willing, able and available for collection of PBMC/ T cells by leucapheresis.
• Hepatitis B and C, HTLV-1, Syphilis, HIV negative.
• Free from serious concurrent illness.
• Female patients of child-bearing age must have a negative pregnancy test and agree to use reliable contraceptive methods for the duration of the therapy and for 6 months afterwards.
• Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards.
• Haematological and Biochemical Indices:
• Haemoglobin (Hb) ≥ 7.0 g/dl; neutrophils ≥ 0.2 x 109/L; total lymphocytes > 0.5 x 109/L; platelets (Plts) ≥ 40 x 109/L
• serum bilirubin, Alanine amino-transferase (ALT) and/or aspartate amino transferase (AST) < 3 x upper normal limit
• calculated creatinine clearance ≥ 30 ml/min (uncorrected value) or isotope clearance measurement ≥ 30ml/min

Further disease specific inclusion criteria are detailed in Protocol

Exclusion criteria

• Age < 18 years or > 75 years.
• Patients should not receive concurrent systemic corticosteroids whilst on the study.
• Within three months of having received fludarabine (at time of leucapheresis).
• Major thoracic and/or abdominal surgery in the preceding three to four weeks from which the patient has not yet recovered.
• Patients who are high medical risks because of non-malignant systemic disease, as well as those with active uncontrolled infection.
• Patients with any other condition, which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
• Patients known to be serologically positive for Hepatitis B, C, HTLV-1 Syphilis or HIV.
• Concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease
• Positive pregnancy test or reluctance to use contraception.
• Pregnant and lactating women are excluded.
• History of Severe Allergy.