Vanderbilt-Ingram Cancer Center

Patients are being asked to take part in this study because they have Acute Myeloid Leukemia (AML). Thirty to 40 % of Acute Myeloid Leukemia (AML) patients above the age of 60 years that enter chemotherapy will attain partial remission or complete remission with incomplete blood count recovery. AML patients who fail to achieve complete remission after first-line therapy have a very poor prognosis and few cures can be achieved at this stage using chemotherapy alone. New approaches to improve life expectancy are thus needed. Active immunization against tumor antigens may be one of these approaches. The tumor antigen targeted in this study is WT1, which is overexpressed and acts as an oncogene in leukemia and in several types of solid tumors. WT1 is not expressed in normal tissues. Early clinical trials using ASCI against leukemia or solid tumors report the induction of immune responses as well as signs of clinical activity against the cancer. Also, no significant toxicities have been reported. This trial will further characterize the immune responses and the clinical activity of this drug. Any toxicities will also be evaluated. At least 40 patients will be enrolled. One group of 20 will include patients in partial remission after induction therapy and another group of 20 will include patients in complete remission but with incomplete blood count recovery. Enrollment in each group will continue until at least 20 patients have received four or more ASCI administrations, and at least 14 patients have received six or more administrations. About 15 centers will take part in this study across the country.

Criteria
 Inclusion Criteria:

 • The patient has cytologically proven AML, as defined by the WHO classification. The pretreatment AML karyotype should be documented.

 • The leukemia is a de novo or secondary AML.

 • The patient's blasts cells show expression of WT1 transcript, detected by quantitative RT-PCR.

 • The patient received the following therapy according to the Institution's standard of care.

 • For patients < 60 years old: at least two induction chemotherapy treatments.

 • For patients >= 60 years old: at least one induction chemotherapy treatment or alternative treatment.

 • The first ASCI administration should be given within 70 days (ten weeks) after the last chemotherapy administration.

 • In the investigator's opinion and in compliance with the Institution Hematology Tumor Board's guidances, the patient should not be eligible for any additional chemotherapy treatment before the ASCI treatment.

 • The clinical status of the patient at inclusion is one of the following (as defined by "Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia" [Cheson, 2003]):

 • Partial Remission (PR) i.e.

 • A decrease of at least 50% in the percentage of blasts to 5%•25% in the bone marrow aspirate following chemotherapy.

 • In case the bone marrow contains <= 5% blasts, the presence of Auer rods also indicates a partial remission.

 • Neutrophil count >= 1,000/μl

 • Platelet count >= 100,000/μl

 • The patient is independent of red blood cell transfusions

 • Morphologic complete remission with incomplete blood count recovery (CRi) i.e. patients fulfil all criteria of the morphological CR except for:

 • Neutrophil count <1,000/μl. and/or

 • Platelet count <= 100,000/μl. However, for the purpose of this clinical protocol platelet levels must be > 50,000/μl.

 • Written informed consent has been obtained prior to the performance of any protocol-specific procedure.

 • The patient is >= 18 years of age at the time of signature of the first informed consent form.

 • Eastern Cooperative Oncology Group performance status of 0, 1 or 2 at the time of enrolment.

 • Adequate hepatic and renal function defined as:

 • Serum bilirubin < 1.5 times the Upper Limit of Normal (ULN).

 • Serum ALT < 2.5 times the ULN.

 • Calculated creatinine clearance > 50 ml/min.

 • In the view of the investigator, the patient can and will comply with the requirements of the protocol.

 • If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to treatment administration, have a negative pregnancy test and continue such precautions for 2 months after completion of the treatment administration series.

 Exclusion Criteria:

 • The patient was diagnosed with leukemic Central Nervous System (CNS) disease (e.g. before chemotherapy) or presents neurological symptoms at baseline suggestive of a CNS involvement.

 • The patient has acute promyelocytic leukemia with t(15;17) (q22;q12), (PML/RARα) or variants.

 • The patient has received, is receiving -or is due to receive- allogeneic SCT.

 • The patient has received Fludarabine, Clofarabine or Cloretazine within 12 months preceding the ASCI treatment.

 • The patient has hypercalcemia.

 • The patient is known to be HIV-positive.

 • The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.

 • The patient has a history of allergic reactions likely to be exacerbated by any component of the study investigational product.

 • The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.

 • The patient has another metastatic cancer disease.

 • The patient has a history of congestive heart failure or previous myocardial infarction.

 • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures.

 • The patient has received any investigational or non-registered medicinal product other than the study treatment within 30 days preceding the first dose of study treatment or plans to receive such a drug during the study period.

 • The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids or any immunosuppressive agents.

 • Note: the use of prednisone, or equivalent, <0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids or topical steroids is permitted.

 • The patient is receiving full dose subcutaneous heparins or is under anti-coagulation treatment (e.g. phenprocoumon).

 • For female patients: the patient is pregnant or lactating.