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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Other: Standard of care; Biological: CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)

Study type: Interventional

Funder types: Other

Identifiers

NCT01995708

13-009

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Arm 1 Vaccine

Experimental group

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.

Treatment:

Biological: CT7, MAGE-A3, and WT1 mRNA-electroporated Langerhans cells ( LCs)

Arm 2 control

Active Comparator group

Description:

Patients receive standard of care treatment after autologous stem cell transplant

Treatment:

Other: Standard of care