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CT7, MAGE-A3, and WT1 mRNA-electroporated Autologous Langerhans-type Dendritic Cells as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

NCT01995708

Description:

The purpose of this study is to see if the investigator can help the immune system to work against myeloma. This study will see if a vaccine made with altered dendritic cells will make T cells work against tumor cells. The stem cells collected for the transplant will also be used to grow dendritic cells in the lab. The dendritic cells will carry the antigens. These cells then will be injected under the skin. The investigators will do lab studies before and after the vaccination to find out if the vaccine is working.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CT7, MAGE-A3, and WT1 mRNA-electroporated Autologous Langerhans-type Dendritic Cells as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
  • Official Title: A Phase I Trial of Vaccination With CT7, MAGE-A3, and WT1 mRNA-electroporated Autologous Langerhans-type Dendritic Cells as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 13-009
  • NCT ID: NCT01995708

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)Arm 1 Vaccine

Purpose

The purpose of this study is to see if the investigator can help the immune system to work against myeloma. This study will see if a vaccine made with altered dendritic cells will make T cells work against tumor cells. The stem cells collected for the transplant will also be used to grow dendritic cells in the lab. The dendritic cells will carry the antigens. These cells then will be injected under the skin. The investigators will do lab studies before and after the vaccination to find out if the vaccine is working.

Trial Arms

NameTypeDescriptionInterventions
Arm 1 VaccineExperimentalThis is a prospective, two-arm phase I randomized trial. Patients will be accrued only from and treated at MSKCCand The Rockefeller University/Center for Clinical & Translational Science . The study will assess autologous LCs presenting CT7, MAGE-A3, and WT1 after electroporation with CT7, MAGE-A3, and WT1 mRNA. Twenty patients will accrue to the study and ten will receive vaccines at 9x10^6 LCs per dose (i.e., combination of 3x10^6 CT7 mRNA-electroporated LCs + 3x10^6 MAGE-A3 mRNA-electroporated LCs + 3x10^6 WT1 mRNA-electroporated LCs) and another ten who will not receive any LC vaccines but will otherwise undergo identical cytoreduction, ASCT, and standard supportive care. At approximately 3 months after ASCT and as deemed clinically appropriate, patients will start lenalidomide maintenance therapy, which is now standard to delay disease progression.
  • CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)
Arm 2 controlActive ComparatorPatients receive standard of care treatment after autologous stem cell transplant

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Symptomatic multiple myeloma, ISS stages I-III, 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.
    
              -  Deemed eligible for ASCT by standard institutional criteria.
    
              -  Age ≥18 years.
    
              -  Documentation of CT7, MAGE-A3, or WT1 expression in the bone marrow and/or bone marrow
                 aspirate.
    
            Exclusion Criteria:
    
              -  Prior autologous or allogeneic SCT.
    
              -  Previous immunization against CT7, MAGE-A3, other cancer-testis antigens, or WT1.
    
              -  Known immunodeficiency, HIV positivity, hepatitis B, or hepatitis C.
    
              -  History of autoimmune disease (e.g., rheumatoid arthritis, SLE), other than vitiligo,
                 diabetes, or treated thyroiditis, which are allowed.
    
              -  History of severe allergic reactions to vaccines or unknown allergens.
    
              -  Participation in any other clinical trial involving another investigational agent
                 within 4 weeks prior to first immunization.
    
              -  Lenalidomide-related toxicities before ASCT necessitating its discontinuation as part
                 of treatment.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:safety
    Time Frame:1 year
    Safety Issue:
    Description:The safety of the vaccine will be monitored and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 for toxicity and adverse event reporting to the Food and Drug Administration. Dose limiting toxicity (DLT) is defined as grade 3 or higher toxicity.The only toxicities captured outside of the SAEs reported will be all grade 1-5 toxicites deemed definitely, probably, or possibly related to the vaccine portion of the study.

    Secondary Outcome Measures

    Measure:Immune response monitoring
    Time Frame:1 year
    Safety Issue:
    Description:The secondary goal of the study is to monitor and compare changes in T cell responses (e.g., intracellular cytokine secretion assays, CTL responses, and immune reconstitution analyses) stimulated by the CT7, MAGE-A3, and WT1 mRNA-electroporated LCs relative to pre-vaccine baselines.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Memorial Sloan Kettering Cancer Center

    Trial Keywords

    • CT7
    • MAGE-A3
    • WT1 mRNA-electroporated Autologous Langerhans
    • vaccine
    • Autologous Stem Cell Transplantation
    • 13-009

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