Pilot Study of recMAGE-A3 + AS15 ASCI as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Multiple Myeloma
- Sponsor
- Ludwig Institute for Cancer Research
- Enrollment
- 13
- Locations
- 4
- Primary Endpoint
- Assessment of Safety of recMAGE-A3 + AS15
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief 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.
Detailed Description
Subjects were enrolled sequentially following confirmation of eligibility criteria, including International Staging System (ISS) stage 1, 2, or 3 multiple myeloma with MAGE-A3 tumor antigen expression. Subjects received a total of 8 immunizations with 300 µg of recMAGE-A3 + AS15. The first immunization was administered approximately 6 to 15 weeks prior to auto-SCT (Day 0), with subsequent immunizations administered every 3 weeks (± 3 days) starting 10 days after auto-SCT (ie, Days 10, 31, 52, 73, and 94). Two additional immunizations were administered at 3-month intervals (± 7 days, ie, Days 180 and 270). No dose adjustments were allowed. Platelet counts must have been ≥ 50 x 10E9/L prior to immunization, with blood product transfusions permitted as necessary. The process for auto-SCT comprised the following: (1) up to 3 steady-state leukopheresis procedures to collect and freeze a sufficient quantity of peripheral blood mononuclear cells (PBMCs), with the first leukopheresis performed 3 weeks (± 6 days) after the first immunization; (2) stem cell mobilization with cyclophosphamide, granulocyte-colony stimulating factor (G-CSF) and/or plerixafor; (3) high-dose melphalan (total dose 200 mg/m2) on Days -3 through -1; (4) auto-SCT on Day 0; and (5) re-infusion with thawed PBMCs on Day 3.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Symptomatic multiple myeloma, ISS stage 1, 2 or 3 within 12 months of starting therapy.
- •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.
- •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.
- •MAGE-A3 expression determined by immunohistochemistry (IHC) present in a bone marrow specimen or plasmacytoma specimen.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •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
Exclusion Criteria
- •Prior treatment with melphalan (Alkeran®), other than 1 cycle (4 days) of oral melphalan.
- •Prior autologous or allogeneic SCT.
- •Prior immunization against MAGE-A3 or other cancer-testis antigens.
- •Concurrent malignancies, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
- •Known immunodeficiency, human immunodeficiency virus (HIV) positivity, or active hepatitis B or C.
- •Known allergy or history of life-threatening reaction to G-CSF or GM-CSF.
- •History of autoimmune disease (eg., rheumatoid arthritis, lupus), other than vitiligo, diabetes, or treated thyroiditis.
- •History of severe allergic reactions to vaccines or unknown allergens.
- •History of myocardial infarction, angina, congestive heart failure, ventricular tachyarrhythmia, stroke or transient ischemic attack within the previous 6 months.
- •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.
Outcomes
Primary Outcomes
Assessment of Safety of recMAGE-A3 + AS15
Time Frame: Continuously for up to 14 months
Analysis of treatment-emergent adverse events (TEAEs) reported from clinical laboratory tests, physical examinations, and vital signs, with severity graded according to the NCI CTCAE, Version 4.0.
Secondary Outcomes
- Induction or Augmentation of MAGE-A3-Specific Humoral Immunity(Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT)
- Induction or Augmentation of MAGE-A3-Specific Cellular Immunity(Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT)
- Assessment of Tumor Response(At 3 and 12 months after auto-SCT)
- Assessment of Survival and Time to Subsequent Therapy(Continuously on study and for up to 5 years post-study)