WT1 Immunity Via DNA Fusion Gene Vaccination in Haematological Malignancies by Intramuscular Injection Followed by Intramuscular Electroporation
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.