NCT01380145

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_1 multiple-myeloma

Timeline
Completed

Started Sep 2011

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 20, 2011

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 27, 2011

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2011

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2014

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

December 22, 2016

Completed
Last Updated

October 25, 2022

Status Verified

October 1, 2022

Enrollment Period

2.8 years

First QC Date

June 20, 2011

Results QC Date

September 7, 2016

Last Update Submit

October 3, 2022

Conditions

Multiple Myeloma

Keywords

multiple myelomaMAGE-A3autologous stem cell transplant

Outcome Measures

Primary Outcomes (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.

    Continuously for up to 14 months

Secondary Outcomes (4)

  • 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

Study Arms (1)

recMAGE-A3 Protein + AS15 Adjuvant

EXPERIMENTAL

Subjects received a total of 8 pre- and post-auto-SCT immunizations with recMAGE-A3 + AS15.

Biological: recMAGE-A3 Protein + AS15 Adjuvant

Interventions

recMAGE-A3 Protein + AS15 AdjuvantBIOLOGICAL

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.

Also known as: Antigen-specific cancer immunotherapeutic (ASCI)
recMAGE-A3 Protein + AS15 Adjuvant

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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)
  • +2 more criteria

You may not qualify if:

  • 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

New York University School of Medicine

New York, New York, 10016, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

  • 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.

    PMID: 30745365DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Results Point of Contact

Title
Jonathan Skipper PhD
Organization
Ludwig Institute for Cancer Research
jskipper@lcr.org
12124501539

Study Officials

  • Hearn J Cho, MD, PhD

    MOUNT SINAI HOSPITAL

    STUDY CHAIR

  • Michael Millenson, MD

    Fox Chase Cancer Center

    PRINCIPAL INVESTIGATOR

  • Nikoletta Lendvai, MD, PhD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 20, 2011

First Posted

June 27, 2011

Study Start

September 1, 2011

Primary Completion

July 1, 2014

Study Completion

November 1, 2014

Last Updated

October 25, 2022

Results First Posted

December 22, 2016

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations

US(4)