Phase II Combination Immunotherapy After ASCT for Advanced Myeloma to Study MAGE-A3 Immunizations With Hiltonol® (Poly-ICLC) Plus Transfer of Vaccine-Primed Autologous T Cells Followed by Lenalidomide Maintenance
18 Years
80 Years
Both
Advanced Myeloma.
Trial Information
Phase II Combination Immunotherapy After ASCT for Advanced Myeloma to Study MAGE-A3 Immunizations With Hiltonol® (Poly-ICLC) Plus Transfer of Vaccine-Primed Autologous T Cells Followed by Lenalidomide Maintenance
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.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
T-Cell responses against the MAGE-3 vaccine
Outcome Description:
T-cell responses against the MAGE-A3 vaccine as measured by proliferation & intracellular cytokine assays, at D100 post-transplant is the primary immunological endpoint.
Outcome Time Frame:
At day 100 post transplant
Safety Issue:
Yes
Principal Investigator
Aaron Rapoport, M.D.
Investigator Role:
Study Chair
Investigator Affiliation:
University of Maryland Greenebaum Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
UPCC 02710
NCT ID:
NCT01245673
Start Date:
November 2010
Completion Date:
November 2013
Related Keywords:
- Advanced Myeloma.
- Advanced Disease
- MAGE-A3 Immunizations with Hiltonol
- Vaccine-Primed Autologous T-Cells
- Lenalidomide Maintenance
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
| University of Maryland Greenebaum Cancer Center | Baltimore, Maryland 21201 |
