MAGE-A3 Protein + AS15 as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Inclusion Criteria:

1. Symptomatic multiple myeloma, ISS stage 1, 2 or 3 within 12 months of starting therapy.
2. Completion of induction therapy with VGPR, or better, by IMWG criteria. All induction myeloma therapy (oral or intravenous, including steroids) must have been discontinued for 3 weeks prior to the first immunization. Subjects did not need to have measurable disease at the time of the screening visit.
3. Signed separate informed consent for stem cell mobilization and high-dose chemotherapy/auto-SCT, and was found to be eligible for SCT by standard institutional criteria.
4. MAGE-A3 expression determined by immunohistochemistry (IHC) present in a bone marrow specimen or plasmacytoma specimen.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
6. The following laboratory parameters within the ranges specified:

   * Neutrophil count: ≥ 1.5 x 109/L
   * Lymphocyte count: ≥ 0.5 x 109/L
   * Platelet count: ≥ 50 x 109/L
   * Serum creatinine: ≤ 2 mg/dL
   * Serum bilirubin: \< 1.5 x the upper limit of normal (ULN)
   * Aspartate and alanine aminotransferase (AST and ALT): \< 2 x ULN
   * Hemoglobin: ≥ 8.0 g/dL
   * International normalized ratio (INR): ≤ 1.5
   * Partial thromboplastin time: ≤ 1.5 x ULN (unless known history of anti-phospholipid antibody or lupus anticoagulant)
7. Age ≥ 18 years.
8. Able and willing to give valid written informed consent.

Exclusion Criteria:

1. Prior treatment with melphalan (Alkeran®), other than 1 cycle (4 days) of oral melphalan.
2. Prior autologous or allogeneic SCT.
3. Prior immunization against MAGE-A3 or other cancer-testis antigens.
4. Concurrent malignancies, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
5. Known immunodeficiency, human immunodeficiency virus (HIV) positivity, or active hepatitis B or C.
6. Known allergy or history of life-threatening reaction to G-CSF or GM-CSF.
7. History of autoimmune disease (eg., rheumatoid arthritis, lupus), other than vitiligo, diabetes, or treated thyroiditis.
8. History of severe allergic reactions to vaccines or unknown allergens.
9. History of myocardial infarction, angina, congestive heart failure, ventricular tachyarrhythmia, stroke or transient ischemic attack within the previous 6 months.
10. Other serious illnesses or co-morbid conditions (e.g., serious infections requiring antibiotics, bleeding disorders, other heart or lung conditions) that, in the opinion of the investigator, made the subject inappropriate for high-dose melphalan and auto-SCT.
11. Pregnancy and breastfeeding.
12. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first immunization.
13. Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
14. Lack of availability for immunological and clinical follow-up assessments.