GVAX vs. Placebo for MDS/AML After Allo HSCT
Condition: Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia
MeSH terms: Leukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes
Intervention: GVAX; Placebo Vaccine; Allogeneic Hematopoietic Stem Cell Transplant; Busulfan; Fludarabine; Tacrolimus; Methotrexate
Intervention description: 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.; 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.; 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).; 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.; 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.; 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.; 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.
Intervention MeSH terms: Methotrexate; Fludarabine; Busulfan; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  AML, CMML-with excess blasts, MDS-RAEB not in remission prior to leukemia cell harvest

          -  HLA 8/8 or 7/8 matched related or unrelated donor available

          -  ECOG performance status of 0-2

          -  Suitable candidate for myeloablative or reduced intensity conditioning allogeneic HSCT
             using PBSC or marrow as stem cell resource

          -  Normal organ function

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Leukemia with active CNS involvement

          -  Positive HIV or HTLV-1 serology

          -  History of allergic reactions to compounds of similar chemical or biologic composition
             to GM-CSF

          -  Uncontrolled intercurrent illness

          -  History of different malignancy except if disease free for at least two years or
             cervical cancer in situ, basal or squamous cell carcinoma of the skin diagnosed and
             treated within the past two years

          -  Prior allogeneic transplant