G-CSF and Plerixafor With Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation for Myeloid Leukemias
The Study Treatment:
Fludarabine is a chemotherapy drug that is designed to make cancer cells less able to repair
damaged DNA (the genetic material of cells). This may increase the likelihood of the cells
Busulfan is a chemotherapy drug that is designed to bind to DNA, which may cause cancer
cells to die. It is commonly used in stem cell transplants.
Plerixafor and filgrastim are designed to cause cancer cells to move from the bone marrow
into the blood stream. This may help to make the cancer cells more sensitive to being
killed by the chemotherapy.
An "allogeneic" (from a donor) stem cell transplant is designed to help the recipient's body
attack the cancer cells that may remain in the body after chemotherapy.
Study Groups and Plerixafor Dose Levels:
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. Up to 4 groups of 3 participants will be enrolled
in the Phase I portion of the study, and up to 48 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of plerixafor you receive will depend
on when you joined this study. The first group of participants will receive the lowest dose
level of plerixafor. Each new group will receive a higher dose of plerixafor than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of plerixafor is found.
If you are enrolled in Phase II, you will receive plerixafor at the highest dose that was
tolerated in the Phase I portion.
In this study, plerixafor is the only study drug where different dose levels are being
tested and compared.
Drug Administration Before the Transplant:
You will receive your first dose of filgrastim on Day -9. (Day -9 means 9 days before the
stem cell transplant, which will occur on Day 0).
Filgrastim is injected under the skin once a day from Day -9 through Day -4. Plerixafor is
injected under the skin once a day from Day -7 through Day -4. The plerixafor injections
will occur 8 hours before the fludarabine and busulfan chemotherapy.
The fludarabine and busulfan will be given by vein through a central venous catheter (CVC).
A CVC is a sterile flexible tube that will be placed into a large vein while you are under
local anesthesia. Your doctor will explain this procedure to you in more detail, and you
will be required to sign a separate consent form for this procedure.
Fludarabine is given once a day from Day -6 through Day -3, over 1 hour each time. On these
same days, busulfan will be given after the fludarabine, over 3 hours.
You will also receive tacrolimus in order to lower the risk of graft vs. host disease
(GVHD). GVHD is a disease that occurs when the donor's immune cells react against the
recipient's body, attacking the recipient's cells and tissues.
Starting on Day -2, tacrolimus will be given as a continuous (non-stop) infusion through the
CVC. When the study doctor decides it seems safe, you will begin taking tacrolimus by mouth
instead, for as long as the study doctor decides is necessary.
If your stem cell donor is not someone who is related to you, you will receive antithymocyte
globulin (ATG) through the CVC once a day from Day -3 through Day -1. On Day -3, it will be
given over at least 6 hours. On Days -2 and -1, it will be given over at least 4 hours.
This drug is given in order to weaken your immune system in order to lower the risk of your
immune system rejecting the transplanted cells.
Blood Tests Before the Transplant:
If you are in the Phase I part of this study, the following blood samples will be drawn and
are not optional. Eight total blood samples (about 1 1/2 teaspoons each) will be drawn
daily with your routine morning labs beginning before your first dose of study therapy (or
Day -9) through Day -3. These samples will be used for research purposes, to study how the
chemotherapy drugs and transplant may affect your normal cells and cancerous cells.
If you are in the Phase II part of the study the following blood samples are optional and if
you agree, eight total blood samples (about 1 1/2 teaspoons each) will be drawn daily
beginning before your first dose of study therapy (or Day -9) through Day -3. These samples
will be used for research purposes, to study how the chemotherapy drugs and transplant may
affect your normal cells and cancerous cells.
Stem Cell Transplant:
On Day 0, after 2 days of rest from chemotherapy, the donor's stem cells will be given to
you by vein (through the CVC). This should take about 30-60 minutes.
Drug Administration After the Transplant:
In addition to continuing to receive tacrolimus to lower the risk of GVHD (as described
above), after the transplant you will also receive methotrexate to lower the risk of GVHD.
Methotrexate will be given by vein, through the CVC, over 15 minutes on Days 1, 3, and 6.
It will also be given on Day 11 if your stem cell donor is someone who is not related to
Once a day, starting at 1 week after the transplant, you will receive filgrastim as an
injection under your skin. These daily injections will continue until your blood counts
Reasons for Stopping the Study Treatment Early:
If you experience intolerable side effects or the disease gets worse during study treatment,
you will be taken off the study treatment.
Other Procedures After the Transplant:
You will remain in the hospital until your blood counts recover (usually about 4 weeks after
the transplant). You will continue being monitored for any infections and
transplant-related side effects for at least 100 days after the transplant.
At 1, 3, 6, and 12 months after the transplant, you will have blood tests (about 3
tablespoons) and bone marrow biopsies performed to check the status of the disease.
Length of Study Participation:
Your active participation in this study will be over at 12 months after the transplant. The
study staff will continue to contact your local doctor regularly from then on. The purpose
is to check the status of the disease and see how you are doing.
This is an investigational study. Busulfan and fludarabine are commercially available and
FDA approved for treating cancer, including AML, MDS, and CML. Filgrastim is commercially
available and FDA approved for the way it is being used in this study (to increase the white
blood cell count). Plerixafor is not FDA approved or commercially available. Using
plerixafor and filgrastim in combination with fludarabine, busulfan, and an allogeneic blood
stem cell transplant in patients with AML, MDS, or CML is not FDA approved. At this time,
the combination is only being used in research.
Up to 72 patients will take part in this study. All will be enrolled at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD) [Plerixafor + Fixed Dose of Filgrastim]
MTD dose of Plerixafor in combination with a fixed dose of Filgrastim where dose limiting toxicity defined as any grade 4 non-hematologic toxicity, observed within 28 days from Day 0 (day of transplant).
28 day cycle (Plerixafor Day -7 to Day -4)
Marina Konopleva, MD, PhD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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