Allogeneic Stem Cell Transplantation, Severe Homzygous 0/+Thalassemia or Sever Variants of Beta 0/+ Thalassemia, THALLO
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | Any - 64 |
| Updated: | 4/21/2016 |
| Start Date: | February 2004 |
| End Date: | May 2016 |
Pilot Study of Allogeneic Stem Cell Transplantation From Unrelated Donors for Patients With Severe Homozygous Beta 0/+ Thalassemia or Severe Variants of Beta 0/+ Thalassemia
Patients have severe beta-thalassemia or one of the thalassemia variants. Thalassemia is a
hereditary disease in which the bone marrow produces abnormal red blood cells that have a
shorter life span than normal red blood cells. Because of that, the patient has chronically
low red blood cell numbers (anemia) and need regular blood transfusions to help the patient
feel better and to help prevent damage to important organs such as the heart. The following
treatments are currently available to patients: lifelong blood transfusions and drugs that
help remove iron from the body, and long-term antibiotics to prevent infections. These
treatments are difficult for patients to take, and do not stop the effects of the disease.
Currently, the only treatment that may cure thalassemia is bone marrow or blood stem cell
transplantation. Special blood or bone marrow cells from a healthy person might allow the
bone marrow to create healthy cells, which will replace the abnormal red blood cells of
thalassemia. There is a lot of experience using special blood or bone marrow cells from a
healthy brother or sister who is the same HLA (immune) type. For patients who do not have
such a donor in the family, an unrelated volunteer donor can be used. It is important for
the patient to realize that this kind of transplant can have more problems than a transplant
from a brother or sister.
Because we do not know the long-term effects of this treatment and because this type of
transplant has not been used often for people with thalassemia, this is a research study. We
hope, but cannot promise, that the transplanted marrow/stem cells will produce healthy cells
and the patient will no longer have severe thalassemia.
hereditary disease in which the bone marrow produces abnormal red blood cells that have a
shorter life span than normal red blood cells. Because of that, the patient has chronically
low red blood cell numbers (anemia) and need regular blood transfusions to help the patient
feel better and to help prevent damage to important organs such as the heart. The following
treatments are currently available to patients: lifelong blood transfusions and drugs that
help remove iron from the body, and long-term antibiotics to prevent infections. These
treatments are difficult for patients to take, and do not stop the effects of the disease.
Currently, the only treatment that may cure thalassemia is bone marrow or blood stem cell
transplantation. Special blood or bone marrow cells from a healthy person might allow the
bone marrow to create healthy cells, which will replace the abnormal red blood cells of
thalassemia. There is a lot of experience using special blood or bone marrow cells from a
healthy brother or sister who is the same HLA (immune) type. For patients who do not have
such a donor in the family, an unrelated volunteer donor can be used. It is important for
the patient to realize that this kind of transplant can have more problems than a transplant
from a brother or sister.
Because we do not know the long-term effects of this treatment and because this type of
transplant has not been used often for people with thalassemia, this is a research study. We
hope, but cannot promise, that the transplanted marrow/stem cells will produce healthy cells
and the patient will no longer have severe thalassemia.
To be treated on this study, we will test the blood to check for viruses, including HIV (the
virus that causes AIDS). If the HIV test is positive, a transplant cannot be done because it
would be too dangerous for the patient. Secondly, we will do a liver biopsy to determine if
the liver has been damaged (which can happen from iron overload that develops after many
transfusions). Too much liver damage could mean that the patient will have a higher risk to
develop problems with the transplant.
To participate in this study, the patients also need to have a central line (a thin plastic
catheter or tube that is placed during surgery into one of the large veins in the neck or
chest). Central lines are used to give intravenous medications (go directly into the vein)
or to take blood samples without the patient having to endure frequent needle sticks. Before
the treatment starts, we will remove a small amount of the bone marrow (back-up bone marrow)
and store it. The reason for this is that if the donors bone marrow or blood stem cells do
not grow properly after the transplant and the patients blood counts stay low, we can put
the patients own bone marrow cells back into their body. This will help the blood counts to
recover, but this means that the patient will also have thalassemia again.
To prepare the body for the transplant, the patients own blood forming system has to be
destroyed and their immune system has to be weakened. To do this, they will be given high
dose chemotherapy and medications that weaken their immune system (also called a
conditioning treatment) for 9 days before the transplant. The main chemotherapy drugs used
in the conditioning treatment are: cyclophosphamide, fludarabine and busulfan. The
chemotherapy treatment will last 9 days. The patient will be admitted 10 days before the
transplant to start a medicine to prevent seizures before they receive the first dose of
busulfan since one of the side effects of busulfan is risk of seizures. First the patient
will be given a drug called busulfan through the central line every 6 hours starting 9 days
before transplant (called Day -9) until 6 days before transplant (called Day -6). Starting
one day after receiving the last busulfan dose (Day -5), they will receive cyclophosphamide,
fludarabine and Campath IH, which will all be given through the central line once a day for
the next four days. Campath IH is a special type of protein called an antibody that works
against certain types of blood cells. Also on Day -5, we will add a drug called MESNA. MESNA
is used to decrease the side-effects caused by cyclophosphamide.
One day after the chemotherapy treatment is finished (Say -1) the patient will have a day to
rest. On Say 0, the patient will receive the bone marrow/stem cells from the donor. Once in
the bloodstream, the cells will go to the bone marrow and should begin to grow. To help
prevent a problem call graft-versus-host disease (GVHD), the patient will receive a small
dose of methotrexate on four different days after transplant. Another drug to help prevent
GVHD, tacrolimus, will be started 2 days (Day -2) before the transplant and continued for
approximately one year after the transplant. To tell whether the transplant has "taken" or
"engrafted", we will take samples of blood two to three weeks after the transplant.
The patient will need to be in the hospital for at least 4 weeks after the transplant to
make sure the transplant has engrafted. To find out how much the treatment has helped them
and how much it might help other patients, we will do several routine lung, kidney, and
liver tests, including liver biopsies, after the bone marrow/stem cell transplant.
Additionally, we will be looking at the immune function. To do this, we will take 30 mL (2
tablespoonfuls) of blood every three months for the first year after transplant and then
every 6 months during the second year after transplant. When possible, the blood that is
taken will be taken through an existing IV line. However, at times drawing the blood will
require another stick with a needle. The total amount of blood to be taken will not exceed
12 tablespoonfuls.
Because bone marrow/stem cell transplant from an unrelated volunteer donor is a new therapy
for severe thalassemia and because problems may happen months afterward, the patient will
need to have exams and blood tests done every few months during the first and second year
following transplantation.
The patient may still need to use iron removing agents for some time after transplant or
undergo blood-letting to get rid of the excess iron in the body. During that time, we will
monitor the amount of iron in the body. Looking at the iron stored in the liver can most
accurately tell us how much excess iron the patient has in the body. We will do liver
biopsies once or twice per year if the patient is receiving iron chelation treatment after
the transplant.
virus that causes AIDS). If the HIV test is positive, a transplant cannot be done because it
would be too dangerous for the patient. Secondly, we will do a liver biopsy to determine if
the liver has been damaged (which can happen from iron overload that develops after many
transfusions). Too much liver damage could mean that the patient will have a higher risk to
develop problems with the transplant.
To participate in this study, the patients also need to have a central line (a thin plastic
catheter or tube that is placed during surgery into one of the large veins in the neck or
chest). Central lines are used to give intravenous medications (go directly into the vein)
or to take blood samples without the patient having to endure frequent needle sticks. Before
the treatment starts, we will remove a small amount of the bone marrow (back-up bone marrow)
and store it. The reason for this is that if the donors bone marrow or blood stem cells do
not grow properly after the transplant and the patients blood counts stay low, we can put
the patients own bone marrow cells back into their body. This will help the blood counts to
recover, but this means that the patient will also have thalassemia again.
To prepare the body for the transplant, the patients own blood forming system has to be
destroyed and their immune system has to be weakened. To do this, they will be given high
dose chemotherapy and medications that weaken their immune system (also called a
conditioning treatment) for 9 days before the transplant. The main chemotherapy drugs used
in the conditioning treatment are: cyclophosphamide, fludarabine and busulfan. The
chemotherapy treatment will last 9 days. The patient will be admitted 10 days before the
transplant to start a medicine to prevent seizures before they receive the first dose of
busulfan since one of the side effects of busulfan is risk of seizures. First the patient
will be given a drug called busulfan through the central line every 6 hours starting 9 days
before transplant (called Day -9) until 6 days before transplant (called Day -6). Starting
one day after receiving the last busulfan dose (Day -5), they will receive cyclophosphamide,
fludarabine and Campath IH, which will all be given through the central line once a day for
the next four days. Campath IH is a special type of protein called an antibody that works
against certain types of blood cells. Also on Day -5, we will add a drug called MESNA. MESNA
is used to decrease the side-effects caused by cyclophosphamide.
One day after the chemotherapy treatment is finished (Say -1) the patient will have a day to
rest. On Say 0, the patient will receive the bone marrow/stem cells from the donor. Once in
the bloodstream, the cells will go to the bone marrow and should begin to grow. To help
prevent a problem call graft-versus-host disease (GVHD), the patient will receive a small
dose of methotrexate on four different days after transplant. Another drug to help prevent
GVHD, tacrolimus, will be started 2 days (Day -2) before the transplant and continued for
approximately one year after the transplant. To tell whether the transplant has "taken" or
"engrafted", we will take samples of blood two to three weeks after the transplant.
The patient will need to be in the hospital for at least 4 weeks after the transplant to
make sure the transplant has engrafted. To find out how much the treatment has helped them
and how much it might help other patients, we will do several routine lung, kidney, and
liver tests, including liver biopsies, after the bone marrow/stem cell transplant.
Additionally, we will be looking at the immune function. To do this, we will take 30 mL (2
tablespoonfuls) of blood every three months for the first year after transplant and then
every 6 months during the second year after transplant. When possible, the blood that is
taken will be taken through an existing IV line. However, at times drawing the blood will
require another stick with a needle. The total amount of blood to be taken will not exceed
12 tablespoonfuls.
Because bone marrow/stem cell transplant from an unrelated volunteer donor is a new therapy
for severe thalassemia and because problems may happen months afterward, the patient will
need to have exams and blood tests done every few months during the first and second year
following transplantation.
The patient may still need to use iron removing agents for some time after transplant or
undergo blood-letting to get rid of the excess iron in the body. During that time, we will
monitor the amount of iron in the body. Looking at the iron stored in the liver can most
accurately tell us how much excess iron the patient has in the body. We will do liver
biopsies once or twice per year if the patient is receiving iron chelation treatment after
the transplant.
Inclusion Criteria:
Patients with documented diagnosis of severe (transfusion-dependent) homozygous
b0/+-thalassemia or severe variants of b0/+-thalassemia requiring chronic transfusion
therapy and iron chelating agents, who fulfill the following conditions:
1. Patient does not have an HLA genotype-identical donor available and has a 5/6 or 6/6
matched unrelated donor, or a 5/6 matched related donor available.
2. Must be between 1 and 16 yrs of age (all Pesaro risk groups).
3. Patients older than 17 yrs of age must be in Pesaro Risk Class 2 or lower (see
Appendix B).
4. Women of childbearing potential must have a negative pregnancy test.
5. Documentation of compliance with iron chelation, absence or presence of hepatomegaly,
and presence or absence of hepatic fibrosis prior to transplant (criteria for the
Pesaro Risk Classification). This information will be obtained by history, physical
exam and interpretation of liver biopsy results.
6. Documentation of awareness of alternative treatment options.
Exclusion Criteria:
1. Biopsy-proven chronic active hepatitis or fibrosis with portal bridging.
2. Has previous history of malignancies.
3. Creatinine clearance < 35 mL/min/1.73 M2.
4. Severe cardiac dysfunction defined as shortening fraction < 25%.
5. HIV infection.
6. Inadequate intellectual capacity to give informed consent (in the case of minors,
this criteria must be fulfilled by the legal guardian).
7. Be pregnant, lactating or unwilling to use appropriate birth control.
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