MAGE-A3 Protein + AS15 as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
|Multiple Myeloma||Biological: recMAGE-A3 Protein + AS15 Adjuvant||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of recMAGE-A3 + AS15 ASCI as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation|
- 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.
- Induction or Augmentation of MAGE-A3-Specific Humoral Immunity [ Time Frame: Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT ]Humoral immunity was determined by enzyme-linked immunosorbent assay (ELISA) to measure the presence of circulating antibodies to MAGE-A3. Titers against an antigen were considered significant if they were >100. Induction of responses was considered significant if there was a change from undetectable (<100) to detectable (>100) or if there was an at least 4-fold increase in titers over time.
- Induction or Augmentation of MAGE-A3-Specific Cellular Immunity [ Time Frame: Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT ]Cellular immunity was determined by enzyme-linked immunosorbent spot assay (ELISPOT) or intracellular flow cytometry to determine peripheral blood levels of interferon gamma-producing CD4+ and CD8+ T cells specific for MAGE-A3. Results were considered significant if > 50 spots and > 2 times the number of spots to negative control were observed.
- Assessment of Tumor Response [ Time Frame: At 3 and 12 months after auto-SCT ]
Tumor responses were evaluated using appropriate imaging methods and were categorized according to the IMWG criteria, which includes the following response designations:
Complete Response (CR): negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% plasma cells in bone marrow; Stringent CR (sCR): CR + normal free light chain (FLC) ratio and absence of clonal cells in bone marrow; Very Good Partial Response (VGPR): Serum/urine M-component detectable by immunofixation but not electropheresis OR ≥90% reduction in serum M-component + urine M-component <100 mg/24 hrs; Partial Response (PR): ≥50% reduction of serum M-protein and reduction in 24-hr urinary M-protein by ≥90% or to <200 mg/24 hrs Stable disease: not response or progression
- Assessment of Survival and Time to Subsequent Therapy [ Time Frame: Continuously on study and for up to 5 years post-study ]Progression-free survival (PFS) was calculated as the date from first immunization to first observation of disease progression or death due to any cause, censored on the start date of subsequent therapy or at the last date of disease assessment for subjects without a PFS event. Overall survival (OS) was calculated as the date from first immunization to death due to any cause, censored at the date of last follow-up for subjects who were alive at the time of the analysis. Time to subsequent therapy was calculated as the date from first immunization to start of subsequent therapy for myeloma, censored at the date of death or last follow-up for subjects who did not receive subsequent therapy.
|Study Start Date:||September 2011|
|Study Completion Date:||November 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Experimental: recMAGE-A3 Protein + AS15 Adjuvant
Subjects received a total of 8 pre- and post-auto-SCT immunizations with recMAGE-A3 + AS15.
Biological: recMAGE-A3 Protein + AS15 Adjuvant
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.
Other Name: Antigen-specific cancer immunotherapeutic (ASCI)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01380145
|United States, New York|
|New York University School of Medicine|
|New York, New York, United States, 10016|
|Mount Sinai Hospital|
|New York, New York, United States, 10029|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111|
|Study Chair:||Hearn J Cho, MD, PhD||Mount Sinai Hospital, New York|
|Principal Investigator:||Michael Millenson, MD||Fox Chase Cancer Center|
|Principal Investigator:||Nikoletta Lendvai, MD, PhD||Memorial Sloan Kettering Cancer Center|