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
This trial can be divided into four phases: 1) Pre-Transplant; 2) Allogeneic Transplant; 3)
Vaccination; and 4) Post-Vaccination Follow-Up.
Phase 1: Pre-Transplant After signing the consent form you will undergo some screening tests
to find out if you can be in this research study. These tests include a medical history,
physical examination, performance status, bone marrow aspirate and biopsy, blood tests,
tuberculosis skin test, HLA antibody test, pregnancy test, urine test, ECHO, MUGA or RVG to
measure heart function, chest x-ray, pulmonary function tests and dental consult. If these
tests show that you are eligible to participate in the research study, you will be enrolled
on the trial and randomized to receive either the GVAX vaccine or the placebo vaccine after
your transplant. After enrolling in the study you will undergo additional research
procedures including a blood draw and leukemia cell collection.
Phase 2: Allogeneic Transplant The transplant phase of the study will begin when you are
admitted to the hospital to receive the chemotherapy and stem cell transplant. In the week
before you receive the stem cells, you will be treated with chemotherapy. The combination of
chemotherapy given before the donor cells are infused is called the conditioning regimen.
The chemotherapy conditioning is given to suppress your immune system so that the donor
blood stem cells will not be rejected after transplantation. The chemotherapy may also
reduce the number of MDS/AML cancer cells in your body.
In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day
or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on your
age and other clinical factors, your transplant doctor will decide whether you receive a
higher or lower dose of busulfan. Between 1-2 days after you finish the chemotherapy, you
will receive the blood stem cell or marrow from your donor. This is given as a transfusion
through a central intravenous line (IV usually placed in your chest or arm).
Just prior to and immediately following the infusion of stem cells, you will receive
medications to help prevent graft-versus-host disease (GVHD), a common complication of
transplant where your donor's immune cells attack your body. The medications you will
receive to prevent GVHD will include Tacrolimus and Methotrexate.
You will be closely monitored as per standard transplant care after your stem cell
transplant. If you received the higher dose chemotherapy conditioning, you will stay in the
hospital for an average of about 3-4 weeks. If you received the lower dose conditioning
transplant, your hospital admission for transplant may be shorter, depending on your
After your stem cell infusion, you may receive daily injections of a medication called
rhGM-CSF, or Leukine, to help your white blood cells to recover faster. You may receive this
medication for up to 2 weeks. You will also be given antiviral and antibiotic medications to
prevent infections as per standard practice after transplantation.
Between 20 to 30 days after your stem cell infusion you will have a physical examination,
routine blood work and a blood draw for future immune tests.
Between 30 to 45 days after your transplant you will return to clinic for a visit that will
include a physical examination, routine blood work, a blood draw for future immune tests and
a bone marrow biopsy and aspirate to assess your MDS/AML.
Phase 3: Vaccination You may begin receiving the GVAX or placebo vaccination between 30 to
45 days following your transplant, provided your blood counts have recovered, and you do not
have any severe side effects from the transplant. If by day 46, your blood counts have not
recovered sufficiently, or if you have developed side effects or GVHD from the transplant,
and do not meed the conditions necessary to start the vaccination portion of this trial,
then you will not receive any vaccinations, and you will be removed from the study. You will
continue to receive standard post transplant care.
If you are able to begin the vaccinations between day 30-45 after your transplant, the GVAC
or placebo vaccine will be administered as an injection under and into the skin on your
forearms or thighs, 6 times over a period of 9 weeks. The first 3 vaccinations will be
administered once a week for 3 consecutive weeks, and the last 3 vaccines will be given once
every other week over 6 weeks. All vaccinations will be given as an outpatient in the
clinic. On the days you are receiving vaccination, you may have to wait several hours in the
clinic while the laboratory makes final preparations on the vaccine/placebo.
During this 9 week period of vaccination, you will continue to be followed by your doctor at
least on a weekly basis to monitor for any transplant of possible vaccine side effects.
Before the first and after the fifth and sixth vaccinations, a small amount of your own
leukemia cells (previously collected before transplant and killed with radiation) will be
injected under your skin (like a TB test) to see if your body will react against it and
cause redness and/or swelling. This is called a delayed-type hypersensitivity (DTH) test.
Two to three days after the DTH test, we would encourage you (but not require you) to return
to the clinic to have a skin biopsy of the DTH injection site. This will allow researchers
to assess whether your new immune system is reacting to the injected leukemia cells under
the microscope. At the same time, we may perform a skin biopsy of the GVAX/Placebo
vaccination site, especially if there is redness or swelling in the area.
During the course of the study, we will also be drawing your blood on a regular basis to
evaluate immune cells and the effect that the vaccinations may have on your new immune
If you tolerate the vaccinations well, and do not have GVHD or any severe side effects from
the transplant or the vaccinations, you will complete a total of 6 vaccines. However, your
vaccination may be terminated earlier if you develop any side effects (from transplant or
vaccination) that do not resolve/improve after 2 weeks, or you develop GVHD that requires
steroid treatment, or if your MDS/AML relapses and you need to receive more treatment.
Phase 4: Post Vaccination Follow-UP About 1 month after your last vaccination, you will have
a physical examination, blood work, immune bloods and bone marrow biopsy and aspirate to
assess the status of your disease.
You will also be followed 6, 9, 12 and 18 months following your transplant with physical
examinations, blood work and immune bloods. At the 12 and 18 month visit you will also ahve
a bone marrow biopsy and aspirate.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Progression Free Survival
Progression-Free Survival (PFS) at 18 months after randomization
Vincent Ho, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|