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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT01995708

Collaborator

(none)

Enrollment

Location

Arms

100.6

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Actual Study Start Date :

Jan 31, 2014

Actual Primary Completion Date :

Jun 20, 2022

Actual Study Completion Date :

Jun 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
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. 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.
Active Comparator: Arm 2 control Patients receive standard of care treatment after autologous stem cell transplant	Other: Standard of care No vaccines

Arm

Intervention/Treatment

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. 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.

Active Comparator: Arm 2 control

Patients receive standard of care treatment after autologous stem cell transplant

Other: Standard of care

No vaccines

Outcome Measures

Primary Outcome Measures

safety [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.

Secondary Outcome Measures

Immune response monitoring [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.