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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Rockefeller University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01995708
First received: November 20, 2013
Last updated: October 6, 2014
Last verified: October 2014
  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.


Condition Intervention Phase
Multiple Myeloma
Biological: CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)
Other: Standard of care
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Immune response monitoring [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 20
Study Start Date: November 2013
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Vaccine
This 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.
Biological: CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)
Patients receive CT7/MAGE-A3/WT1 mRNA-electroporated autologous Langerhans-type dendritic cells ID on days 12, 30, and 90 after autologous stem cell transplant.
Active Comparator: Arm 2 control
Patients receive standard of care treatment after autologous stem cell transplant
Other: Standard of care
No vaccines

  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 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.
  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: NCT01995708

Contacts
Contact: David Chung, MD PhD 212-639-6617
Contact: James Young, MD 646-888-2052

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: David Chung, MD, PhD    212-639-6617      
Contact: James Young, MD    646-888-2052      
Principal Investigator: David Chung, MD, PhD         
The Rockefeller University/Center for Clinical & Translational Science Recruiting
New York, New York, United States, 10065
Contact: David Chung, MD, PhD    212-639-6617      
Principal Investigator: David Chung, MD, PhD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Rockefeller University
Investigators
Principal Investigator: David Chung, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01995708     History of Changes
Other Study ID Numbers: 13-009
Study First Received: November 20, 2013
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CT7,
MAGE-A3
WT1 mRNA-electroporated Autologous Langerhans
vaccine
13-009

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

ClinicalTrials.gov processed this record on November 20, 2014