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Multiple MyelomaPhase 1NCT01380145

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

A Phase 1 study testing recMAGE-A3 Protein + AS15 Adjuvant in people with Multiple Myeloma, run by Ludwig Institute for Cancer Research at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
recMAGE-A3 Protein + AS15 Adjuvant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
4 sitesUnited States
Study dates
Sep 2011to Nov 2014
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 1.
  • The following laboratory parameters within the ranges specified:
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  • 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)
  • Age ≥ 18 years.
  • Able and willing to give valid written informed consent.

Who cannot join

  • 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.
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  • 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.
  • Pregnancy and breastfeeding.
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first immunization.
  • Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability for immunological and clinical follow-up assessments.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • New York University School of Medicine

    New York, New York, 10016

  • Mount Sinai Hospital

    New York, New York, 10029

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: Pilot Study of recMAGE-A3 + AS15 ASCI as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

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.

Read the 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.

Being tested
recMAGE-A3 Protein + AS15 Adjuvant
Keywords
multiple myeloma, MAGE-A3, autologous stem cell transplant
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • recMAGE-A3 Protein + AS15 AdjuvantBiological

    Also called Antigen-specific cancer immunotherapeutic (ASCI)

    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.

Study groups in NCT01380145
Study groupRoleWhat they receive
recMAGE-A3 Protein + AS15 AdjuvantExperimentalSubjects received a total of 8 pre- and post-auto-SCT immunizations with recMAGE-A3 + AS15.
Receives: Biological: recMAGE-A3 Protein + AS15 Adjuvant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of Safety of recMAGE-A3 + AS15

    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.

    Measured: Continuously for up to 14 months

Secondary outcomes (4)

  1. Induction or Augmentation of MAGE-A3-Specific Humoral Immunity

    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.

    Measured: Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT

  2. Induction or Augmentation of MAGE-A3-Specific Cellular Immunity

    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.

    Measured: Baseline, first immunization, and first and second leukopheresis prior to auto-SCT; Days 31, 73, 194, 284, and 374 after auto-SCT

  3. Assessment of Tumor Response

    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

    Measured: At 3 and 12 months after auto-SCT

  4. Assessment of Survival and Time to Subsequent Therapy

    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.

    Measured: Continuously on study and for up to 5 years post-study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionJul 2014
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01380145
Sponsor's protocol ID
LGS 2009-005
Other IDs
10-051, 10-216
Status last verified
Oct 2022
First submitted
20 Jun 2011
Last updated
25 Oct 2022
Data monitoring committee
No
Individual data sharing
No

Publications

  • Cohen AD, Lendvai N, Nataraj S, Imai N, Jungbluth AA, Tsakos I, Rahman A, Mei AH, Singh H, Zarychta K, Kim-Schulze S, Park A, Venhaus R, Alpaugh K, Gnjatic S, Cho HJ. Autologous Lymphocyte Infusion Supports Tumor Antigen Vaccine-Induced Immunity in Autologous Stem Cell Transplant for Multiple Myeloma. Cancer Immunol Res. 2019 Apr;7(4):658-669. doi: 10.1158/2326-6066.CIR-18-0198. Epub 2019 Feb 11.

    PubMed 30745365

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing recMAGE-A3 Protein + AS15 Adjuvant in people with Multiple Myeloma, run by Ludwig Institute for Cancer Research at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of Safety of recMAGE-A3 + AS15 (time frame: Continuously for up to 14 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01380145, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022.

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