WT1 Immunity Via DNA Fusion Gene Vaccination in Haematological Malignancies by Intramuscular Injection Followed by Intramuscular Electroporation (WIN)

Inclusion Criteria:

• CML patients:

Philadelphia chromosome positive CML in chronic phase, in complete cytogenetic response (CCyR) but with detectable BCR-ABL transcripts and maintained the CCyR on imatinib monotherapy for a minimum of 24 months

AML patients:

WT1+ AML in CR or morphologic CR with incomplete blood count recovery (CRi);

All patients:

• ≥ 18 years of age, written informed consent
• Performance status of 0 or 1.
• for vaccination groups: HLA-A0201 positive in at least one allele
• for control groups: HLA A2 negative in both alleles
• renal function and liver function (Creatinine <1.5 x upper limit of normal, liver function tests < 1.5 x upper limit of normal); Lymphocyte count > 1.0 x109/l; normal clotting
• HB>100 g/l
• Adequate venous access for repeated blood sampling according to protocol schedule.
• If sexually active and possibly fertile, patients must agree to use appropriate contraceptive methods during the trial and for six months afterwards.

Exclusion Criteria:

• CML patients:

  • CML in accelerated phase or blast crisis or having achieved CMR at any point during imatinib therapy.
  • Imatinib dose modification in the previous year, Imatinib interruption for more than 15 days in the previous 6 months to enrolment
  • Prior interferon-α therapy
  • hypocellular bone marrow (<20%)
  • Complete molecular response (CMR)

AML patients:

• AML in haematological relapse or eligible for allogeneic SCT.
• hypocellular bone marrow (<20%)
• AML patients with the "good-risk" abnormalities comprised by the core binding factor leukaemias (i.e., AML with the translocation (8;21) and inversion of chromosome 16, and acute promyelocytic leukaemia with the translocation (15;17))

All patients:

• Systemic steroids or other drugs with a likely effect on immune competence are forbidden during the trial. The predictable need of their use will preclude the patient from trial entry
• Major surgery in the preceding three to four weeks from which the patient has not yet recovered.
• Patients who are of high medical risk 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, such as concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease
• Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.
• Patients who are serologically positive for or are known to suffer from Hepatitis B, C, Syphilis or HIV. Counselling will be offered to all patients prior to testing.