Back to resultsCT7, MAGE-A3, and WT1 mRNA-electroporated Autologous Langerhans-type Dendritic Cells as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)
Standard of care
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring CT7, MAGE-A3, WT1 mRNA-electroporated Autologous Langerhans, vaccine, Autologous Stem Cell Transplantation, 13-009
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.
Sites / Locations
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm 1 Vaccine
Arm 2 control
Arm Description
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.
Patients receive standard of care treatment after autologous stem cell transplant
Outcomes
Primary Outcome Measures
safety
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
Immune response monitoring
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.
Full Information
NCT ID
NCT01995708
First Posted
November 20, 2013
Last Updated
June 22, 2022
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT01995708
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
January 31, 2014 (Actual)
Primary Completion Date
June 20, 2022 (Actual)
Study Completion Date
June 20, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
CT7, MAGE-A3, WT1 mRNA-electroporated Autologous Langerhans, vaccine, Autologous Stem Cell Transplantation, 13-009
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 Vaccine
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2 control
Arm Type
Active Comparator
Arm Description
Patients receive standard of care treatment after autologous stem cell transplant
Intervention Type
Biological
Intervention Name(s)
CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)
Intervention Description
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. Patients on the vaccine arm of the study will receive a total of 3 vaccinations, comprising a primary immunization on day +12 after ASCT followed by two boosters at days +30 and +90. Vaccines will be dosed at 9x10^6 LCs per vaccine x 3.
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
No vaccines
Primary Outcome Measure Information:
Title
safety
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Immune response monitoring
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.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Chung, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35100339
Citation
Chung DJ, Sharma S, Rangesa M, DeWolf S, Elhanati Y, Perica K, Young JW. Langerhans dendritic cell vaccine bearing mRNA-encoded tumor antigens induces antimyeloma immunity after autotransplant. Blood Adv. 2022 Mar 8;6(5):1547-1558. doi: 10.1182/bloodadvances.2021005941.
Results Reference
derived
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
CT7, MAGE-A3, and WT1 mRNA-electroporated Autologous Langerhans-type Dendritic Cells as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
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