Myeloma
Conditions
Keywords
Advanced Disease, MAGE-A3 Immunizations with Hiltonol, Vaccine-Primed Autologous T-Cells, Lenalidomide Maintenance
Brief summary
One purpose of this study is to find out if a new combination of immune system treatments (MAGE-A3 vaccine plus activated T-cells) will allow the body to build up protection (immunity) against the myeloma cells. A second purpose is to find out how well this combination of immune system treatments is able to control the myeloma.
Detailed description
Autologous stem cell transplant (ASCT) can lead to a complete or partial disappearance of the myeloma in about 2 out of 3 patients. However, an ASCT only sometimes leads to a cure of the myeloma. In about half the patients the myeloma comes back after about 1-2 years. In about 90% of patients it comes back by about 10 years after transplant. One possible way to improve upon the results of ASCT for myeloma is to help the body's defense or immune system recover faster after transplant. Another way is to teach the body's immune system to fight against the myeloma cells. In two earlier research studies which included more than 100 patients, certain types of immune cells called T cells or T lymphocytes were taken out of a patient's body using a procedure called apheresis. These cells were then grown up in the lab. After the transplant, these T cells were put back into the patients. The replaced T cells helped the patients'immune systems to recover faster after the transplant. In addition, when the T cells were given back to patients they also received a vaccination. The vaccination or injection was for a certain type of pneumonia germ called pneumococcus. We found that most patients built up protection against this pneumonia-causing germ. In another study, we used a possible myeloma cancer vaccine. However, we found that less than half the patients responded to this vaccine. In this new study, we want to test a different type of myeloma cancer vaccine. This different cancer vaccine is based on a protein called MAGE-A3. The MAGE-A3 protein is found in about 50% of cases of myeloma. This vaccine consists of small pieces of protein (called peptides) which come from the MAGE-A3 protein. In order to help the immune system respond better we will add two new steps. First we will add an immune system stimulant called Hiltonol® to each vaccination. Hiltonol® is a chemical substance that turns on several parts of the immune system. It may make the immune system better able to respond to the vaccine. It has been tested in several hundred patients and has been used with about a dozen different types of cancer and germ vaccines. Second, starting about 100 days after the transplant procedure, patients will get a medicine called Lenalidomide. Lenalidomide is already approved by the Food and Drug Administration (FDA) for treatment of myeloma. In this study, we want to know whether Lenalidomide could help to improve the body's ability to respond to the vaccinations and help to treat the myeloma itself.
Interventions
OTHERActivated/costimulated autologous T-cell
For all patients, the cells will be expanded ex vivo for up to 12 days and then prepared for infusion \ day 2 post-transplant. The target number of costimulated T-cells for infusion will be \ 5 x 10e10 T-cells total in 100-500 mL total volume.
BIOLOGICALPrevnar- Pneumococcal Conjugate Vaccine (PCV)
After study enrollment, patients will receive Prevnar- Pneumococcal Conjugate Vaccine (PCV). At Day #14, Day #42, and Day #90, Day #120 and Day #150, patients will receive a booster immunization with Prevnar- Pneumococcal Conjugate Vaccine (PCV).
DRUGRevlamid® (Lenalidomide)
At about day 100 post-transplant, after completion of post-transplant immunological assessments and myeloma restaging studies, patients will be eligible to receive low-dose Revlamid® (Lenalidomide) 10 mg/day for maintenance therapy (10 mg/day) until progression of myeloma or development of intolerance.
BIOLOGICALMAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)
After study enrollment, patients will receive both MAGE-A3/GM-CSF \[+ coinjection of 2mg of Hiltonol®(Poly-ICLC)\]. At Day #14, Day #42, Day #90, Day #120 and Day #150 patients will receive an additional immunization with MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC).
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Patients must be registered with the Sponsor's Monitor * Patients must have a diagnosis of myeloma * Patients must meet one of the following criteria: 1. Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy). 2. Myeloma has responded partially to initial therapy but a complete response (immunofixation negative and normal serum free light chain studies)has NOT developed after a minimum of 3 cycles or months of initial therapy. 3. Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard autotransplants:complex karyotype (\> or = to 3 abnormalities),t(4;14),t(14;16),del (17)(p13.1),and/or chromosome 13 abnormalities. * Patients must have measurable disease on study entry * Patients must be between ages 18-80 (inclusive). * Patients should have adequate vital organ function as defined by the protocol. * ECOG performance status 0-2 (unless due solely to bone pain) * Prior to Lenalidomide maintenance phase, all study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test as per the protocol * Lenalidomide treatment phase: able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
Exclusion criteria
* Pregnant or nursing females * HIV or HTLV-1/2 seropositivity * Known history of myelodysplasia * Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy). * Active Hepatitis B (as defined by + Hepatitis B surface antigen); + Hepatitis C virus (HCV) antibody is NOT an exclusion * Prior autotransplant or allogeneic transplant * More than 4 distinct, prior courses of therapy for myeloma * History of severe autoimmune disease requiring steroids or other immunosuppressive treatments. * Active immune-mediated diseases including:connective tissue diseases, uveitis,sarcoidosis,inflammatory bowel disease, multiple sclerosis. * Evidence or history of other significant cardiac,hepatic,renal, ophthalmologic,psychiatric,or gastrointestinal disease which would likely increase the risks of participating in the study * Active bacterial, viral or fungal infections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Myeloma Endpoint | Between day 100 and 180 post transplant | To determine whether lenalidomide maintenance plus the late booster immunizations leads to improved myeloma clinical responses between day 180 and day 100 post-transplant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prevnar, T Cells, Lenalidomide, MAGE A-3 MAGE-A3, GM-CSF, Hiltonol® (Poly-ICLC), PCV vaccine prior to apheresis.
Stem cell mobilization. High-dose melphalan, then hematopoietic stem cells on Day 0.
Day 2 Activated/costimulated autologous T cells.
Days 14, 42 and 90 MAGE-A3, Hiltonol® and PVC.
Day 100 start Lenalidomide.
Day 120 and 150 MAGE-A3 and PVC. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| MAGE-A3, Hiltonol®, PVC After T Cells | Off Study due to Disease Progression | 1 |
Baseline characteristics
| Characteristic | Prevnar, T Cells, Lenalidomide, MAGE A-3 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 52.48 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 9 / 27 |
Outcome results
Primary
Primary Myeloma Endpoint
To determine whether lenalidomide maintenance plus the late booster immunizations leads to improved myeloma clinical responses between day 180 and day 100 post-transplant.
Time frame: Between day 100 and 180 post transplant
Population: Subjects that reached D100 and D180
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects with poorer response at D100 and D180 | 4 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects in CR D100 and D180 | 4 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects in sCR D100 and 180 | 1 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects in VGPR D100 and D180 | 1 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects in PR D100 and D180 | 5 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects with SD at D+100 and 180 | 3 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects with improved response at D100 and D180 | 6 Participants |
| Prevnar, T Cells, Lenalidomide, MAGE A-3 | Primary Myeloma Endpoint | Subjects with no disease response reported | 2 Participants |