Multiple Myeloma
Conditions
Keywords
CT7, MAGE-A3, WT1 mRNA-electroporated Autologous Langerhans, vaccine, Autologous Stem Cell Transplantation, 13-009
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.
Interventions
BIOLOGICALCT7, 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.
OTHERStandard of care
No vaccines
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Evaluated for Vaccine Safety | 1 year | Participants will be evaluated for the safety of the vaccine, 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
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival | Up to 7 years | Median profression free survival. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 13 |
| Arm 2 Control Patients receive standard of care treatment after autologous stem cell transplant
Standard of care: No vaccines | 15 |
| Total | 28 |
Baseline characteristics
| Characteristic | Arm 1 Vaccine | Total | Arm 2 Control |
|---|---|---|---|
| Age, Continuous | 58 years | 59 years | 62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 24 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 21 Participants | 12 Participants |
| Region of Enrollment United States | 13 Participants | 28 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 10 Participants | 24 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 12 / 13 | 8 / 15 |
| other Total, other adverse events | 13 / 13 | 15 / 15 |
| serious Total, serious adverse events | 3 / 13 | 2 / 15 |
Outcome results
Primary
Number of Participants Evaluated for Vaccine Safety
Participants will be evaluated for the safety of the vaccine, 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Vaccine | Number of Participants Evaluated for Vaccine Safety | 13 Participants |
| Arm 2 Control | Number of Participants Evaluated for Vaccine Safety | 15 Participants |
Secondary
Median Progression Free Survival
Median profression free survival.
Time frame: Up to 7 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 Vaccine | Median Progression Free Survival | 31 months |
| Arm 2 Control | Median Progression Free Survival | 54 months |