A 3-Arm Randomized Phase II Study of Standard-of-Care vs. Bortezomib Based Graft-Versus-Host Disease Regimen for Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation Patients Lacking HLA-matched Related Donors
You will undergo some screening tests or procedures to find out if you can be in this
research study. Many of these tests and procedures are likely to be part of regular cancer
care and may be done even if it turns out that you do not take part in the research study.
If you have had some of these tests or procedures recently, they may or may not have to be
repeated. Possible tests include a medical history, physical exam, laboratory tests,
pulmonary function tests, cardiac ejection fraction and a pregnancy test. If these tests
show that you are eligible to participate in the research study, you will begin the study
treatment. If you do not meet the eligibility criteria, you will not be able to participate
in the research study.
Because no one knows which of the study options is best, you will be "randomized" into one
of the study groups (described below). Randomization means that you are put into a group by
chance. It is like flipping a coin. You will have an equal chance of being placed in any of
Before your transplant you will receiving conditioning therapy. The conditioning therapy for
this study involves fludarabine and busulfex. These drugs will be given five, four, three
and two days before your transplant (Days -5 through -2). Both these chemotherapy drugs are
commonly used in allogeneic stem cell transplantation. On Day 0, you will receive selected
blood cells taken from your sibling or unrelated donor.
You will receive 1 of 3 GVHD prophylaxis plans depending on which one you are randomized to:
- Group 1 will receive tacrolimus + methotrexate
- Group 2 will receive bortezomib + tacrolimus + methotrexate
- Group 3 will receive bortezomib + sirolimus + tacrolimus
Tacrolimus (Groups 1 and 2) will be started three days before your transplant (Day -3). You
will be given tacrolimus initially intravenously (through a needle in a vein in your arm or
through a "central line", a catheter or tube placed in the large vein under your collarbone
or your neck) and later by mouth. You will continue to take tacrolimus for 3 to 6 months
after your transplant. Your physician will discuss your tacrolimus dose with you.
Methotrexate (Groups 1 and 2) will be given intravenously one, three, six and eleven days
after your transplant (Days 1,3,6 and 11).
Bortezomib (Groups 2 and 3) will be given intravenously one, four and seven days after your
transplant (Days 1,4 and 7).
Sirolimus (Group 3 only) will start three days before your transplant (Day -3). You will be
given sirolimus initially intravenously and then later by mouth. You will need to continue
to take your sirolimus for 3 to 6 months after your transplant. Your physician will discuss
your sirolimus dose with you.
To help with engraftment, you will be given the drug G-CSF (Neupogen) starting the day after
your transplant, until your white blood cells recover. You will receive other medications as
part of standard of care to help prevent you from getting infections. You will also receive
medications to help prevent seizures during your conditioning therapy.
Each week for the first four weeks and 2,3,6 and 12 months following your transplant, you
will have a physical exam and you will be asked questions about your general health and
specific questions about any problems that you might be having and any medications you may
be taking. If you are taking bortezomib, you will have an exam and may be asked to fill out
an additional questionnaire about potential symptoms of numbness, tingling, weakness or pain
on days 1,4 and 7 after your transplant.
Each week for the first four weeks and 12 months following your transplant, you will have
blood drawn (approximately 6 teaspoons) to monitor your progress and health following
transplant. If you receive methotrexate and/or bortezomib, you will have an additional blood
draw on those days.
Approximately 12 months following your transplant, a needle will be inserted into your hip
bone and a small amount of bone marrow cells and a sample of bone are removed.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine incidence of grade II-IV GVHD
To determine the incidence of grade II-IV acute GVHD by day 180 after stem cell infusion.
John Koreth, DPhil, MBBS
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Brigham and Women's Hospital||Boston, Massachusetts 02115|
|Dana-Farber Cancer Insitute||Boston, Massachusetts 02115|