Busulfan-Fludarabine-Clofarabine With Allogeneic Stem Cell Transplantation for Advanced Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Advanced, Gleevec Refractory Chronic Myeloid Leukemia. A Randomized Phase II Study.
Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA (the genetic
material of cells). Clofarabine is designed to interfere with the growth and development of
cancer cells. Fludarabine is designed to interfere with DNA repair enzymes so that the
leukemic cells cannot repair damaged DNA. This may increase the likelihood of the cell
dying. These drugs are being given to try to kill cancerous cells and weaken your immune
system in order to lower the risk of stem cell transplant rejection.
If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of a coin) to 1 of 4 study groups. Three (3) of the groups will receive
busulfan, fludarabine, and clofarabine at different dose levels. The 4th group will only
receive busulfan and clofarabine. As the study continues, participants will be assigned
using a method called adaptive randomization. This method works by increasing the chances
of being assigned to the group that has had the best results in the study so far. You will
know which group you have been assigned to.
Participants will receive busulfan, fludarabine, and/or clofarabine once a day for 4 doses.
You will first receive an additional low-level "test" dose of busulfan given by vein to
check how your blood levels change over time. This information will be used to decide the
next dose needed to reach a target blood level of busulfan. You will have a total of about
6 and 1/2 tablespoons of blood drawn over time to check your busulfan blood levels following
one or more of the busulfan treatments. Up to 11 samples of blood will be drawn to check
your blood levels of busulfan during the next 11 hours following the test dose and the first
high-dose busulfan treatment. Each sample will require about 1 teaspoon of blood. A
heparin lock line will be placed in a vein to lower the number of needle sticks needed for
these draws. If it is not possible for these blood level tests to be performed for
technical or scheduling reasons, you will receive the standard fixed (unchanging) dose of
Clofarabine and fludarabine (if applicable) will be given through a central venous catheter
(CVC) over 1 hour, once a day, for 4 days. Busulfan will also be given through the CVC over
If you are going to be receiving a transplant from an HLA-nonidentical or unrelated donor,
you will also receive thymoglobulin (ATG) over 4 hours on the 3 days before the transplant
to further weaken your immune system to reduce the risk of rejecting of the transplant.
After the transplant, you will receive tacrolimus, methotrexate, or other immunosuppressive
(lowering the immune system) drugs in the standard manner to lower the risk of graft-vs-host
disease (GVHD), a reaction of the donor's immune cells against the recipient's body.
The allogeneic stem cells (bone marrow or peripheral blood stem cells) will also be given
through the CVC. You will receive the drug G-CSF (filgrastim) as an injection under the
skin once a day, starting 1 week after the transplant, until your blood cell levels return
Patients usually stay in the hospital for about 4 weeks after stem cell transplantation.
After you are released from the hospital, you will continue to be monitored as an outpatient
for infections and transplant-related complications for at least 100 days after the
You will have blood tests (about 4 tablespoons of blood) and bone marrow aspirations
performed at 1, 3, 6, and 12 months after the transplant, to check if the disease is in
remission (has not come back). Your health status will be followed with the help of your
local doctor to find out if the leukemia or MDS comes back, as well as to check the length
of your survival.
This is an investigational study. All of the drugs used in this study are approved by the
FDA for treatment of cancer. Busulfan has been approved for use in stem cell
transplantation. The use of these drugs together with stem cell transplant is experimental.
Up to 70 patients will take part in this study. All will be enrolled at the M. D. Anderson
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Optimal Dose Level
Four combinations of daily doses to be studied in 4 day schedule
Richard E. Champlin, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
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