Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma
|ClinicalTrials.gov Identifier: NCT01245673|
Recruitment Status : Active, not recruiting
First Posted : November 22, 2010
Last Update Posted : December 20, 2017
|Condition or disease||Intervention/treatment||Phase|
|Myeloma||Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV) Other: Activated/costimulated autologous T-cell Drug: Lenalidomide Biological: MAGE-A3, Hiltonol® (Poly-ICLC)||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||April 2011|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||August 2018|
|Experimental: Prevnar, T Cells, Lenalidomide, MAGE A-3||
Biological: Prevnar- Pneumococcal Conjugate Vaccine (PCV)
On day +2 all patients will receive ~ 5 x 10e10 costimulated T-cells which have been primed in vivo with MAGE-A3/ Hiltonol® and PCV.Other: Activated/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. On the designated infusion date, the T-cells will be harvested.Drug: 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 lenalidomide for maintenance therapy (10 mg/day) until progression of myeloma or development of intolerance.Biological: MAGE-A3, Hiltonol® (Poly-ICLC)
After study enrollment, patients will receive both MAGE-A3/GM-CSF [+ coinjection of 2mg of Hiltonol®(Poly-ICLC)]
- T-Cell responses against the MAGE-3 vaccine [ Time Frame: At day 100 post transplant ]T-cell responses against the MAGE-A3 vaccine as measured by proliferation & intracellular cytokine assays, at D100 post-transplant is the primary immunological endpoint.
- Change in Paraprotein Levels [ Time Frame: 180 Days Post-Transplant ]We will also compare the paraprotein levels in the blood or urine by SPEP/UPEP and serum free light chain analyses at day 100 post-transplant to the levels at day +180 post-transplant. We would like to demonstrate that the overall response rate (PR + near-CR + CR) is > 20% greater at day +180 than at day +100.
- MAGE-A3 Immune Responses [ Time Frame: Day 180 post-transplant ]A secondary endpoint will be the comparison of MAGE-A3 immune responses at day 180 post-transplant vs day 100 post-transplant to evaluate immune potentiation effect of lenalidomide.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01245673
|United States, Maryland|
|University of Maryland Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||Aaron Rapoport, M.D.||University of Maryland Greenebaum Cancer Center|
|Principal Investigator:||Ed Stadtmauer, MD||Abramson Cancer Center of the University of Pennsylvania|