Lentivirus Transduced Acute Myeloid Leukaemia Blasts Expressing B7.1 (CD80) and IL-2 (RFUSIN2-AML1)

The purpose of this study is to assess the safety and tolerability of an 'AML Cell Vaccine' in patients with poor prognosis acute myeloid leukaemia (AML).

• Biological: RFUSIN2-AML1
  AML cell vaccine alone. x4 doses 3 weeks apart
  Other Name: RFUSIN2-AML1
• Biological: Donor leukocyte infusion (DLI)
  1 dose 1x107/kg
  Other Name: RFUSIN2-AML1
• Biological: RFUSIN2-AML1 and donor leukocyte infusion
  AML cell vaccine x 4 doses 3 weeks apart Donor leukocyte infusion 1x107/kg x 1 dose
  Other Name: RFUSIN2-AML1
• Biological: RFUSIN2-AML1 and donor leukocyte infusion
  AML cell vaccine x4 doses 3 weeks apart Donor leukocyte infusion 1x108/kg x1 dose
  Other Name: RFUSIN2-AML1

• Experimental: cohort 1
  AML Cell Vaccine alone
  Intervention: Biological: RFUSIN2-AML1
• Experimental: cohort 2
  Donor leukocytes alone
  Intervention: Biological: Donor leukocyte infusion (DLI)
• Experimental: cohort 3
  AML cell vaccine and Donor Leukocyte Infusion (1x107/kg)
  Intervention: Biological: RFUSIN2-AML1 and donor leukocyte infusion
• Experimental: cohort 4
  AML cell vaccine and Donor Leukocyte Infusion (1x108/kg)
  Intervention: Biological: RFUSIN2-AML1 and donor leukocyte infusion

Inclusion Criteria:

• Diagnosis of AML defined according to the WHO classification
• Age ≥ 18 years
• New presentation or relapsed AML
• Patients must be able to give written informed consent
• Failure to enter complete morphological remission (>5% bone marrow AML cells) or persistence of cytogenetic abnormality following intensive combination chemotherapy At day+100 post-transplant
• HIV negative
• No GvHD
• No continuing use of immunosuppressive drugs
• Absence of active systemic fungal or viral infection including HTLV-1, hepatitis B or C.
• Adequate renal and liver function confirmed by: creatinine clearance >30mls/min; bilirubin <3.0 x upper limit of normal; AST <3.0 x upper limit of normal; prothrombin time <2.0 x upper limit of normal.

Performance status of 1 or less by ECOG criteria or >80% by the Karnovsky score

• Patient must provide written informed consent and be willing to comply for the duration of the study.
• Life expectancy >36 weeks
• Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 10 - 14 days and again within 24 hours of starting the study. In addition, sexually active WCBP must agree continued abstinence from heterosexual intercourse or to use adequate contraceptive methods starting 4 weeks prior to the initiation of therapy (see appendix G for pregnancy testing and birth control guidelines while on study). WCBP must agree to have pregnancy tests every 3 weeks while on study drug (every 14 days for women with irregular cycles) and 4 weeks after the last dose of study drug. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy.

Exclusion Criteria:

• Age < 18 years
• Patients not fit for intensive chemotherapy
• Complete morphological and cytogenetic remission following intensive combination chemotherapy
• Absence of HLA compatible donor
• HIV positive
• Evidence of graft versus host disease at day+100 post transplant
• Evidence of relapse of leukaemia (≥5% bone marrow blasts)
• Concurrent use of other forms of anti-leukaemic therapy
• Other malignancy with the exception of carcinoma in situ.
• Significant history of heart disease (unstable angina, myocardial within the past six months, congestive cardiac failure requiring daily treatment)
• Evidence of active lung disease determined by chest x-ray and absence of chronic lung disease (FEV1<60% predicted, Vital capacity <60%, Tlco<50%)

• Department of Health
• Leukemia Research Fund
• Elimination of Leukaemia Fund