Trial Information

Unrelated Donor Reduced Intensity Bone Marrow Transplant for Children With Severe Sickle Cell Disease (BMT CTN #0601)

SCD is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and
intense episodes of pain, also called "sickle cell crises." SCD is caused by an abnormal
type of hemoglobin, which is a protein inside red blood cells that carries oxygen to vital
organs, such as the brain, heart, lungs, and kidneys. Defective hemoglobin damages red blood
cells. The damaged cells, in turn, can block blood flow in vessels and block oxygen and
nutrients from reaching organs. For people with severe forms of SCD, one treatment option is
a bone marrow transplant, which may correct the abnormal blood cell production problem. In
most cases, bone marrow transplants are performed in people who have a healthy sibling with
the same tissue type. If people do not have a sibling with the same tissue type, it is
possible for them to receive a blood stem cell transplant from an unrelated donor through
bone marrow transplant .

Traditionally, people with SCD who are undergoing a bone marrow transplant receive high
doses of chemotherapy and medications before the transplant as part of the conditioning
regimen to prepare their immune system to accept the donor cells. Participants will
experience fewer side effects with a reduced intensity conditioning regimen than with a more
intense conditioning regimen. The purpose of this study is to determine the safety and
effectiveness of blood stem cell transplants, using bone marrow from unrelated donors, in
children with severe SCD who receive a reduced intensity conditioning regimen before the
transplant. Specifically, researchers will evaluate whether the reduced intensity
conditioning regimen is successful in allowing donor cells to settle and grow successfully,
in preventing the production of SCD-damaged red blood cells, and in limiting SCD-related
organ damage.

This study will enroll children with severe SCD who lack a sibling with the same tissue type
who can serve as their donor. Participants will attend a study visit prior to the transplant
to undergo a blood collection, neurocognitive testing to measure learning and brain
function, and magnetic resonance angiogram (MRA) and magnetic resonance imaging (MRI) scans.
Questionnaires to assess quality of life will also be completed. Twenty-two days before the
transplant, participants will begin receiving a reduced intensity conditioning regimen of
chemotherapy and medications to prepare them for the transplant. Eight days before the
transplant, participants will be admitted to the hospital and will continue the conditioning
regimen. Participants will then receive the bone marrow transplant. After the transplant,
participants will receive immunosuppression medications for at least 6 months to prevent
graft-versus-host disease (GVHD), which may occur if the immune cells from the donated bone
marrow attacks the body of the recipient. One week after the transplant, participants will
receive granulocyte-colony-stimulating factor (G-CSF), which is a natural protein that
increases the white blood cell count and helps protect the body against infections.
Participants will receive G-CSF until their white blood cell level is normal again.
Participants will remain in the hospital and be closely monitored for signs of infection or
other complications until study researchers feel it is safe for them to return home.

After leaving the hospital, participants will attend study visits weekly during Weeks 1 to
8, at Day 60, weekly during Weeks 9 to 14, at Day 100, at Month 6, and at Years 1 and 2. At
all study visits, a blood collection, medical history review, and physical exam will occur.
In addition, at Day 100, Month 6, and Years 1 and 2, questionnaires to assess quality of
life will be completed. At select visits the following procedures will also occur: lung
function testing, heart function testing, MRA and MRI scans, and neurocognitive testing.