Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation With Bevacizumab for Advanced Solid Tumor
The Study Drugs:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.
The combination of standard chemotherapy drugs (fludarabine and melphalan) used for this
study may help to improve the chances of your body accepting the stem cell transplant.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic
material of cells) and weaken the immune system so that stem cells can stay in your body.
Melphalan is designed to damage the cancer cells' DNA.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will have a central venous
catheter inserted. A central venous catheter 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.
You will receive chemotherapy with bevacizumab, fludarabine, and melphalan in order to
prepare for the stem cell transplant.
On Day 1, you will receive bevacizumab through a needle in your vein over 30 minutes.
On Days 2-6, you will receive fludarabine by vein over 30 minutes.
On Day 5-6, you will receive melphalan by vein over 30 minutes.
On Day 7, you will receive no study drugs.
Stem Cell Transplant and Post-Transplant Drug Administration:
On Day 8, you will have a stem cell transplant. Your study doctor will explain this
procedure to you in more detail and you will sign a separate consent form.
After the transplant, you will receive the drugs tacrolimus and methotrexate. Tacrolimus
and methotrexate are used to prevent graft versus host disease (GVHD), a condition that
occurs when the transplanted cells attack the normal cells in the body.
Tacrolimus will be given by vein non-stop (24 hours a day) until you are able to take
medications by mouth. Once you are able to take medications by mouth, your doctor will tell
you how and when to take the oral medication. You will receive tacrolimus for 2-3 months.
During the last month that tacrolimus is given, the dose will be lowered gradually.
Methotrexate will be given by vein over a few seconds on Days 9, 11, and 14. An additional
dose of methotrexate will be given on Day 19 if your donor is your parent, child, or an
unrelated family member.
If GVHD does occur, the GVHD will be treated with methylprednisolone by vein or by mouth, as
needed. You may also be given steroid cream to use on the skin, if needed.
Starting at least 3 weeks after the transplant, as soon as your blood counts recover, you
will receive bevacizumab every 2 weeks by vein over 30 minutes.
You must stay in the hospital for about 3-4 weeks beginning on Day 1. While you are in the
hospital, blood (about 2 teaspoons) will be drawn for routine tests every day.
You must stay in the Houston area for about 100 days after the transplant. Once a month
during the 100 days after the transplant, and then every 3 months for the first year, you
will have scans to check the status of the disease. The study doctor will decide which
scans are necessary (chest x-rays, CT scans, and/or bone scans). You may also have a bone
marrow aspirate and biopsy at these times. The bone marrow aspirate and biopsy would only
be performed if your bone marrow was shown to be involved with the disease at the time of
If the disease is still present at 2 months after the transplant, and you do not have GVHD,
you will stop receiving tacrolimus within 2 weeks. After that, if the disease is still
present after another 6 weeks, and you do not have GVHD, you may receive an infusion of
donor lymphocytes (a type of white blood cell) by vein over about 30 minutes. This treatment
with white blood cells may be repeated 2 more times with 6 weeks between each infusion.
Length of Study:
You will be taken off-study after 1 year.
You will have follow-up visits as per standard of care.
This is an investigational study. The use of bevacizumab in transplant patients is not FDA
approved. Melphalan and fludarabine are FDA approved and commercially available for
transplant patients. Up to 18 patients will take part in this study. All will be enrolled
at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression-free Survival (PFS)
Number or participants with no disease progression or death for any reason during first 100 days following transplantation. Participants followed every 3 months for first year.
100 days after transplant
Naoto Ueno, MD, PhD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|U.T.M.D. Anderson Cancer Center||Houston, Texas 77030|