Evaluating the Safety and Effectiveness of Bone Marrow Transplants in Children With Sickle Cell Disease (BMT CTN 0601)
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Hematopoietic Stem Cell Transplantation
Intervention type(s): Biological
Intervention description(s): The stem cell transplant preparative regimen is listed below. Day 0 is the day of the transplant. The - sign is the number of days before and the + sign is the number of days after the transplant.
Alemtuzumab: Children weighing 10 kg or more will receive 10 mg, 15 mg, and 20 mg intravenously (IV) on Days -21, -20, and -19, respectively
Fludarabine: 30 mg/m^2/day IV on Days -8 through -4
Melphalan: 140 mg/m^2 IV on Day -3
Rest on Days -2 and -1
Transplant occurs on Day 0
GVHD prophylaxis: Tacrolimus or cyclosporine beginning Day -3, methotrexate (7.5 mg/m2/day) Day 1, 3 and 6 and methylprednisolone/prednisone on Day +7 to +28 followed by a taper if there is no GVHD
Other intervention name(s): Bone Marrow Transplant
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Sickle Cell Disease; Sickle Cell Anemia