Evaluating the Safety and Effectiveness of Bone Marrow Transplants in Children With Sickle Cell Disease (BMT CTN 0601)



Status:Completed
Conditions:Anemia, Hematology
Therapuetic Areas:Hematology
Healthy:No
Age Range:3 - 19
Updated:5/12/2018
Start Date:August 2008
End Date:September 2016

Use our guide to learn which trials are right for you!

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

Sickle cell disease (SCD), also known as sickle cell anemia, is an inherited blood disease
that can cause organ damage, stroke, and intense pain episodes. A blood stem cell transplant
is a treatment option for someone with a severe form of the disease. Prior to undergoing a
transplant, people typically receive a conditioning regimen of high doses of chemotherapy and
other medications to prepare the body to accept the transplant. A conditioning regimen that
uses lower doses of chemotherapy and medications may be safer for transplant recipients. This
study will evaluate 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 prior to the transplant.

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.

Inclusion Criteria:

- SCD (genotype hemoglobin SS disease [Hb SS], genotype hemoglobin SC disease
[HbSC],sickle ß°[Sß°] thalassemia, or sickle ß^+[Sß^+]thalassemia) with one or more of
the following:

1. Patients must have symptomatic SCD (genotype Hb SS, Hb SC, Sß° thalassemia or Sß+
thalassemia), AND have 1 or more of the following clinical complications:(i)
Clinically significant neurologic event (stroke) or any neurologic deficit
lasting more than 24 hours that is accompanied by an infarct on cerebral MRI; OR
(ii) patients who have a Transcranial Doppler (TCD) velocity that exceeds 200
cm/sec by the non-imaging technique (or TCD measurement greater than 185 cm/sec
by the imaging technique) measured at a minimum of 2 separate occasions one month
or more apart; OR,

2. Minimum of two episodes of acute chest syndrome in the 2 years before study
entry, defined as new pulmonary alveolar consolidation involving at least one
complete lung segment (associated with acute symptoms including fever, chest
pain, tachypnea, wheezing, rales, or cough that is not attributed to asthma or
bronchiolitis) despite adequate supportive care measures

3. History of 3 or more severe pain events per year in the 2 years before study
entry

- Lansky/Karnofsky performance score greater than or equal to 40

- Patients must have an unrelated adult bone marrow donor who is Human Leukocyte Antigen
(HLA)-matched at 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based
typing.

- Patients with adequate physical function: a)Cardiac: Left ventricular ejection
fraction (LVEF) greater than 40%, or LV shortening fraction greater than 26%; b)
Pulmonary: Pulse oxymetry with a baseline O2 saturation of greater than or equal to
85% is required for all patients, Carbon Monoxide Diffusing Capacity (DLCO) greater
than 40% (corrected for hemoglobin) for patients in whom pulmonary function testing
can be performed; c) Renal: Serum creatinine less than or equal to 1.5 x upper limit
of normal for age and glomerular filtration rate (GFR) greater than 100 mL/min/1.73 m.
For patients older than or equal to 16 years of age, GFR should be greater than 70
mL/min/1.73 m^2; d) Hepatic: Serum conjugated (direct) bilirubin less than 2x upper
limit of normal for age as per local laboratory; alanine transaminase (ALT) and
aspartate transaminase (AST) less than 5 times upper limit of normal as per local
laboratory.

- If the patient has been receiving chronic transfusion therapy for more than or equal
to 1 year AND has clinical evidence of iron overload (serum ferritin level of greater
than 1000 ng/ml), a liver biopsy shall be obtained within 90 days of starting
conditioning therapy (alemtuzumab). Histologic exam of the liver must document absence
of bridging fibrosis or cirrhosis of the liver. In other cases, a liver biopsy is
optional.

- Hemoglobin S (Hb S) level less than or equal to 45%, seven days prior to initiation of
alemtuzumab

Exclusion Criteria:

- Evidence of uncontrolled bacterial, viral or fungal infections (currently taking
medication and progression of clinical symptoms) within 1 month prior to starting the
conditioning regimen. Patients with fever or suspected minor infection should await
resolution of symptoms before starting the conditioning regimen

- Pregnant or breastfeeding

- Patients with 8/8 HLA-matched family donors able to donate

- Seropositivity for HIV

- Prior allogeneic marrow or stem cell transplant

- Iron chelation must be discontinued more than or equal to 48 hours before initiating
the conditioning regimen

- Hydroxyurea (if receiving this therapy) must be discontinued more than or equal to 48
hours before initiating the conditioning regimen
We found this trial at
21
sites
New Hyde Park, New York 11040
?
mi
from
New Hyde Park, NY
Click here to add this to my saved trials
1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
2500 N State St
Jackson, Mississippi 39216
(601) 984-1000
University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
?
mi
from
Jackson, MS
Click here to add this to my saved trials
2500 N State St
Jackson, Mississippi 39216
(601) 984-1000
University of Mississippi Medical Center The University of Mississippi Medical Center, located in Jackson, is...
?
mi
from
Jackson, MS
Click here to add this to my saved trials
Miami, Florida 33124
(305) 284-2211
University of Miami A private research university with more than 15,000 students from around the...
?
mi
from
Miami, FL
Click here to add this to my saved trials
Ann Arbor, Michigan 48109
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
1405 Clifton Road NE
Atlanta, Georgia 30322
404-785-6000
Children's Healthcare of Atlanta Whether treating a toddler in an emergency or supporting a teen...
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
101 Manning Dr
Chapel Hill, North Carolina 27599
(919) 966-4131
University of North Carolina Hospital at Chapel Hill The UNC Health Care System is a...
?
mi
from
Chapel Hill, NC
Click here to add this to my saved trials
171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
?
mi
from
Charleston, SC
Click here to add this to my saved trials
225 E Chicago Ave
Chicago, Illinois 60611
(312) 227-4000
Ann & Robert H. Lurie Children's Hospital of Chicago Ann & Robert H. Lurie Children
?
mi
from
Chicago, IL
Click here to add this to my saved trials
11100 Euclid Ave
Cleveland, Ohio 44106
(216) 844-1000
University Hospitals of Cleveland The history of University Hospitals Case Medical Center is linked to...
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
?
mi
from
Houston, TX
Click here to add this to my saved trials
Kansas City, Missouri 64108
?
mi
from
Kansas City, MO
Click here to add this to my saved trials
8701 W Watertown Plank Rd
Milwaukee, Wisconsin
(414) 955-8296
Medical College of Wisconsin The Medical College (MCW) of Wisconsin is a major national research...
?
mi
from
Milwaukee, WI
Click here to add this to my saved trials
New Orleans, Louisiana 70118
?
mi
from
New Orleans, LA
Click here to add this to my saved trials
630 W 168th St
New York, New York
212-305-2862
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
?
mi
from
New York, NY
Click here to add this to my saved trials
3414 Fifth Avenue
Pittsburgh, Pennsylvania 15213
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
Richmond, Virginia 23298
(804) 828-0100
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
?
mi
from
Richmond, VA
Click here to add this to my saved trials
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials
111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
?
mi
from
Washington,
Click here to add this to my saved trials
111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
?
mi
from
Washington,
Click here to add this to my saved trials