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:07/20/2023
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
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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.
- 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:
- Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy
- Recurrent acute chest syndrome with significant respiratory compromise each time
- Sickle nephropathy
- Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity
- Red cell alloimmunization with the need for chronic transfusions
- 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.
- 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
- 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)