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

Phase 2
3 Years
19 Years
Open (Enrolling)
Sickle Cell Disease

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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.

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 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

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

- Patients must have an unrelated adult BM bone marrow donor who is 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, 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 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; ALT and
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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Outcome Time Frame:

Measured at Year 2

Safety Issue:


Principal Investigator

Shalini Shenoy, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Washington University School of Medicine


United States: Federal Government

Study ID:




Start Date:

August 2008

Completion Date:

June 2015

Related Keywords:

  • Sickle Cell Disease
  • Sickle Cell Disease
  • Sickle Cell Anemia
  • Anemia, Sickle Cell



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University of Michigan Medical Center Ann Arbor, Michigan  48104-0914
Texas Transplant Institute San Antonio, Texas  78229
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Cook Children's Medical Center Fort Worth, Texas  76104
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