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

• ClinicalTrials.gov Identifier: NCT01995708
• Recruitment Status: Completed
• First Posted: November 26, 2013
• Last Update Posted: June 23, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: November 20, 2013
• First Posted Date: November 26, 2013
• Last Update Posted Date: June 23, 2022
• Actual Study Start Date: January 31, 2014
• Actual Primary Completion Date: June 20, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 10, 2015)

safety [ Time Frame: 1 year ]

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.

Original Primary Outcome Measures (submitted: November 25, 2013)

safety [ Time Frame: 1 year ]

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.

Current Secondary Outcome Measures (submitted: November 25, 2013)

Immune response monitoring [ Time Frame: 1 year ]

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• 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. 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.
• Other: Standard of care
  No vaccines

Study Arms

• 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.
  Intervention: Biological: CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)
• Active Comparator: Arm 2 control
  Patients receive standard of care treatment after autologous stem cell transplant
  Intervention: Other: Standard of care

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 6, 2018): 28
• Original Estimated Enrollment (submitted: November 25, 2013): 20
• Actual Study Completion Date: June 20, 2022
• Actual Primary Completion Date: June 20, 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01995708
• Other Study ID Numbers: 13-009
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: David Chung, MD, PhD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: June 2022