MAGE-A3 Protein + AS15 as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: recMAGE-A3 Protein + AS15 Adjuvant
Intervention description: recMAGE-A3 + AS15 was administered intramuscularly at a dose of 300 µg recMAGE-A3, with no dose adjustments permitted. The first immunization was administered 6 to 15 week prior to auto-SCT, with subsequent immunizations administered on Days 10, 31, 52, 73, and 94 (± 3 days) and Days 180 and 270 (± 7 days) after auto-SCT.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: multiple myeloma; MAGE-A3; autologous stem cell transplant

Summary:

      This was an open-label, single-arm, pilot study of the recombinant MAGE-A3 protein plus the
      immunological adjuvant AS15 (recMAGE-A3 + AS15) in subjects with symptomatic multiple myeloma
      who had completed induction therapy with at least a Very Good Partial Response (VGPR) by the
      International Myeloma Working Group (IMWG) criteria and who were eligible for high-dose
      chemotherapy with autologous stem cell transplant (auto-SCT). The primary objective was to
      determine the safety and tolerability of immunizations when administered prior to stem cell
      mobilization and multiple times after stem cell reinfusion. Secondary objectives were to
      assess the humoral and cellular immunogenicity and clinical outcomes of immunization.
    

Eligibility criteria:

        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.