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Phase I-II

A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders

  • Study HIC#:2000025196
  • Last Updated:05/24/2024

This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.

  • Age21 years and younger
  • GenderBoth

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Trial Purpose and Description

Patients < 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan.

This will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.

Eligibility Criteria

Inclusion Criteria:

  • Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy
  • For patients with sickle cell disease, must have one of the following severe manifestations:
    1. Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy
    2. Recurrent acute chest syndrome with significant respiratory compromise each time
    3. Sickle nephropathy
    4. Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity
    5. Red cell alloimmunization with the need for chronic transfusions
    6. Recurrent osteonecrosis or multiple joint involvement from avascular necrosis
  • Patients with sickle cell disease must have hemoglobin S < 30% within 30 days prior to beginning alemtuzumab
  • Age </= 20.99 years at the time of enrollment
  • Performance score > 50
  • Left ventricular ejection fraction > 40% or left ventricular shortening fraction > 26% by echocardiogram
  • DLCO > 40% (corrected for hemoglobin) or pulse oximetry with a baseline O2 saturation of >/= 90% on room air if too young to perform PFTs
  • Serum creatinine < 1.5x upper limit of normal for age and/or GFR > 70 mL/min/1.73m2
  • Direct bilirubin < 2x upper limit of normal for age
  • ALT and AST < 5x upper limit of normal for age
  • Participants who have or are receiving >/= 8 packed red blood cell transfusions for >/= 1 year or >/= 20 packed red blood cell transfusions (lifetime cumulative) will undergo liver MRI for estimation of hepatic iron content.
    1. Liver biopsy is indicated for hepatic iron content >/= 7mg Fe/mg liver dry weight by liver MRI.

Histologic examination of the liver must document for the absence of cirrhosis, bridging fibrosis, and active hepatitis

Exclusion Criteria:

  • Patients who have an HLA-identical sibling who is able and willing to donate bone marrow
  • Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis
  • Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment
  • Evidence of HIV infection or known HIV positive serology
  • Patients who have received a previous stem cell transplant
  • Patients who have received an investigational drug or device or off-label use of a drug or device within 3 months of enrollment
  • Females who are pregnant or breast feeding
  • Patients with active autoimmune disease (e.g. sarcoidosis, lupus, scleroderma)

Principal Investigator


For more information about this study, including how to volunteer, contact: