GVAX vs. Placebo for MDS/AML After Allo HSCT
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational intervention to learn whether the intervention, in this case, the GVAX vaccine, works in preventing your MDS or AML from relapsing after your allogeneic stem cell transplantation. "Investigational" means that the vaccine is still being studied and that research doctors are trying to find out more about it-such as the side effects it may cause, and if the vaccine is effective. It also means that the FDA has not yet approved the vaccine for your type of cancer.
You are being asked to participate in this trial because you have advanced myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Your doctor has determined that you are a candidate for an allogeneic stem cell transplant as treatment for your MDS/AML. Allogeneic stem cell transplantation is a standard treatment for MDS/AML. It can be effective because the cells from your donor (also known as the graft) could form a new immune system that can fight against the MDS/AML cells in your body. This is also known as the "graft-versus-leukemia" or "GVL" effect. In patients with advanced MDS or AML that is not in remission at the time of transplantation, as in your case, relapse remains the number one cause of transplant failure. As such, this clinical trial is designed to assess whether adding a leukemia vaccine early after transplantation could stimulate donor cells to fight your cancer and improve transplant outcomes.
In recent years, researchers at the Dana-Farber Cancer Institute have discovered that GVAX, a vaccine made from the patient's own cancer cells engineered to produce a protein called GM-CSF, can be effective in stimulating a powerful immune response specific to that cancer. GM-CSF is a naturally occurring hormone in the body that helps the immune system fight infections and diseases. The GVAX vaccine is made in the laboratory by using a virus (called adenovirus, which has been modified so it cannot cause illness) to insert the GM-CSF gene into tumor cells. The cells are then irradiated, which prevents them from being able to grow, before being administered to patients in a series of vaccinations.
A previous phase I clinical trial using this GVAX vaccine in patients with MDS/AML after allogeneic transplantation demonstrated that the GVAX vaccine is safe, and the survival outcomes were encouraging. The current randomized phase II study will investigate this vaccine further and gather more information to assess the activity.
If you participate in this research study, you will be "randomized" to receive either GVAX vaccination or placebo (a saline solution) vaccination. Randomization means that you are put into a group by chance. It is like flipping a coin. There is a 50% chance that you will receive the GVAX vaccine and a 50% chance you will receive placebo. Neither you nor your transplant doctor(s) will know which you will be receiving.
The primary goal of this trial is to assess if there will be a difference in the percentage of cancer free survivors in the vaccinated vs. placebo group at 18 months after transplant.
Acute Myeloid Leukemia
Biological: Placebo Vaccine
Procedure: Allogeneic Hematopoietic Stem Cell Transplant
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized Placebo-controlled Phase II Trial of Irradiated, Adenovirus Vector Transferred GM-CSF Secreting Autologous Leukemia Cell Vaccination (GVAX) Versus Placebo Vaccination in Patients With Advanced MDS/AML After Allogeneic Hematopoietic Stem Cell Transplantation|
- Progression Free Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]Progression-Free Survival (PFS) at 18 months after randomization
- Safety and toxicity of vaccination, as measured by the development of grade II-IV and III-IV acute graft versus host disease, CTC grade 3 and higher non-hematologic toxicity, or grade 4 and higher hematologic toxicity attributable to vaccination [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Assessment of the safety of vaccination following allogeneic (ablative or reduced intensity) stem cell transplantation
- Incidence of acute and chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessment of incidence fof grade 2-4 and grade 3-4 acute GVHD, and chronic GVHD after vaccination following allogeneic stem cell transplantation
- PFS after start of vaccination [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessment of PFS after start of vaccination
- Relapse and non-relapse mortality [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessment of relapse and non-relapse mortality after vaccination
- Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessment of overall survival after vaccination
- Biologic activity of GVAX vs. Placebo as assessed by laboratory and histologic analyses of blood before and after vaccination. [ Time Frame: 2 years ] [ Designated as safety issue: No ]Assessment of the biologic activity of GVAX as compared to placebo vaccination after HSCT
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Active Comparator: GVAX
|Biological: GVAX Procedure: Allogeneic Hematopoietic Stem Cell Transplant Drug: Busulfan Drug: Fludarabine Drug: Tacrolimus Drug: Methotrexate|
Placebo Comparator: Placebo
|Biological: Placebo Vaccine Procedure: Allogeneic Hematopoietic Stem Cell Transplant Drug: Busulfan Drug: Fludarabine Drug: Tacrolimus Drug: Methotrexate|
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|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Vincent Ho, MD||Dana-Farber Cancer Institute|