GVAX vs. Placebo for MDS/AML After Allo HSCT

Summary

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 MDS, CMML, or AML from relapsing after 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 these types of cancer.

Participants are being asked to participate in this trial because they have advanced myelodysplastic syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), or acute myeloid leukemia (AML). Investigators have determined that participants are a candidate for an allogeneic stem cell transplant as treatment for MDS/CMML/AML. Allogeneic stem cell transplantation is a standard treatment for MDS/CMML/AML. It can be effective because the cells from the donor (also known as the graft) could form a new immune system that can fight against the MDS/CMML/AML cells in the body. This is also known as the "graft-versus-leukemia" or "GVL" effect. In patients with advanced MDS, CMML, or AML that is not in remission at the time of transplantation, 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 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.

Participants in this study will be "randomized" to receive either GVAX vaccination or placebo (a saline solution) vaccination. Randomization means participants are put into a group by chance. It is like flipping a coin. There is a 50% chance they will receive the GVAX vaccine and a 50% chance they will receive placebo. Neither participants nor investigators will know which participants 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.

Conditions

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia

Interventions

BIOLOGICAL

GVAX

GVAX or placebo vaccination will begin between 30 to 60 days following participant's transplant, provided participant meets vaccination initiation criteria. Only participants in the GVAX arm will receive GVAX vaccine.

BIOLOGICAL

Placebo Vaccine

GVAX or placebo vaccination will begin between 30 to 60 days following participant's transplant, provided participant meets vaccination initiation criteria. Only participants in the placebo arm will receive placebo vaccine.

PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplant

Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor. This is given as a transfusion through a central intravenous line (IV usually placed in the chest or arm).

DRUG

Busulfan

In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 5 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.

DRUG

Fludarabine

In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 5 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.

DRUG

Tacrolimus

Just prior to and immediately following the infusion of stem cells, the participant will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the recipient's body. The medications the participant will receive to prevent GVHD will include: * Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months. * Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.

DRUG

Methotrexate

Just prior to and immediately following the infusion of stem cells, the participant will receive medications to help prevent graft-versus-host disease (GVHD), a common complication of transplant where the donor's immune cells attack the recipient's body. The medications the participant will receive to prevent GVHD will include: * Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months. * Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.

Sponsors & Collaborators

• Massachusetts General Hospital

  collaborator OTHER

• Beth Israel Deaconess Medical Center

  collaborator OTHER

• Dana-Farber Cancer Institute

  lead OTHER

Principal Investigators

• Vincent Ho, MD · Dana-Farber Cancer Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-01-08

Primary Completion

2020-12-11

Completion

2021-11-24

Countries

• United States

Study Locations