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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT01380145
First received: June 20, 2011
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

This study seeks to assess the safety and immunogenicity of recombinant MAGE-A3 protein plus AS15 Adjuvant in patients with symptomatic multiple myeloma, who have completed induction therapy with at least Very Good Partial Response and who are eligible for high dose chemotherapy with autologous stem cell transplant.


Condition Intervention Phase
Multiple Myeloma
Biological: recMAGE-A3 Protein plus AS15 Adjuvant
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • Assess safety and tolerability according to the National Cancer Institute CTCAE v4.0 [ Time Frame: Up to 14 months ] [ Designated as safety issue: Yes ]
    Laboratory tests, vital sign measurements, physical exams and patient histories will be performed to detect new abnormalities and deteriorations of any pre-existing conditions


Secondary Outcome Measures:
  • Induction or augmentation of MAGE-A3-specific humoral immunity [ Time Frame: Baseline. Day 45, 24 & 10 prior to Stem Cell Transplantation. Day 31, 73 194, 284 & 374 after Stem Cell Transplantation ] [ Designated as safety issue: No ]
    Humoral Immunity will be determined by ELISA assays to measure antibodies to MAGE-A3.

  • Assess tumor response and disease progression in accordance with the established International Myeloma Working Group (IMWG) criteria [ Time Frame: Up to 14 months ] [ Designated as safety issue: No ]
    Three and 12-month response category, progression free-survival, time to next treatment, and overall survival will be assessed.

  • Induction or augmentation of MAGE-A3-specific cellular immunity [ Time Frame: Baseline. Day 45, 24 & 10 prior to Stem Cell Transplantation. Day 31, 73 194, 284 & 374 after Stem Cell Transplantation ] [ Designated as safety issue: No ]
    Cellular Immunity will be determined by ELISPOT or intracellular flow cytometry


Estimated Enrollment: 16
Study Start Date: June 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: recMAGE-A3 Protein plus AS15 Adjuvant Biological: recMAGE-A3 Protein plus AS15 Adjuvant
Eight intramuscular immunizations with 300 mcg recMAGE-A3 Protein plus AS15 Adjuvant
Other Name: ASCI

Detailed Description:

Open label, single arm pilot study of recombinant MAGE-A3 protein plus AS15 Adjuvant (recMAGE-A3 + AS15 ASCI) in 16 patients with symptomatic multiple myeloma, ISS stage 1, 2 or 3, who have completed induction therapy with at least Very Good Partial Response (VGPR) by International Myeloma Working Group (IMWG) criteria, and who are eligible for high dose chemotherapy with autologous stem cell transplant (auto-SCT) by standard institutional criteria. MAGE-A3 tumor antigen expression will be required for study entry. Patients will receive 8 immunizations over 320 days, with the first immunizations given approximately 6 weeks before auto-SCT, and the rest given post-SCT

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Symptomatic multiple myeloma, ISS stage 1, 2 or 3 within 12 months of starting therapy.
  • Completion of induction therapy with Very Good Partial Response (VGPR), or better, by International Myeloma Working Group (IMWG) criteria. All induction myeloma therapy (oral or intravenous, including steroids) must be discontinued for 3 weeks prior to first immunization. Patients do not need to have measurable disease at the time of this screening visit.
  • Has signed separate informed consent for stem cell mobilization and high dose chemotherapy/autologous stem cell transplant, and is found to be eligible for stem cell transplant by standard institutional criteria.
  • MAGE-A3 expression determined by IHC must be present in a bone marrow specimen or plasmacytoma specimen.
  • ECOG performance status 0-1 .
  • The following laboratory parameters must be 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 up to 1.5 x ULN for lab, AST and ALT up to 2 x ULN for lab, Hemoglobin ≥ 8.0 g/dL, INR ≤ 1.5, Partial thromboplastin time ≤ 1.5 x ULN for lab unless known history of anti-phospholipid antibody or lupus anticoagulant)
  • Age ≥ 18 years.
  • Able and willing to give valid written informed consent.

Exclusion Criteria:

  • Prior treatment with melphalan (Alkeran®), other than 1 cycle (4 days) of oral melphalan.
  • Prior autologous or allogeneic stem cell transplant.
  • Previous 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, HIV positivity, Hepatitis B or Hepatitis 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, which are allowed.
  • 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 past 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 make the patient inappropriate for high-dose melphalan and autologous stem cell transplant.
  • Pregnancy and breastfeeding.
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first immunization.
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability for immunological and clinical follow-up assessment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01380145

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
New York University Cancer Institute
New York, New York, United States, 10016
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Ludwig Institute for Cancer Research
GlaxoSmithKline
Investigators
Study Chair: Hearn J Cho, MD, PhD Mount Sinai School of Medicine
Principal Investigator: Adam D Cohen, MD Fox Chase Cancer Center
Principal Investigator: Nikoletta Lendvai, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

No publications provided

Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT01380145     History of Changes
Other Study ID Numbers: LGS 2009-005, 10-051, 10-216
Study First Received: June 20, 2011
Last Updated: July 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 01, 2014