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

About the study

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.

Study point of contact

Stephanie Hyde, CCRP
Shalini Shenoy, MD


2 United States sites


1 Day - 21 Years


Phase 1/Phase 2

Study type






participation requirements

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 /= 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 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

Female subjects of childbearing potential, must agree to practice 2 methods of contraception at the same time from the time of signing of informed consent through 12 months post transplant. Male subjects must agree to practice effective barrier contraception or practice true abstinence from the time of signing informed consent through 12 months post transplant.
Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution’s Human Studies Committee.

participation restrictions

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)


  • New Haven, Connecticut, United States, Yale School of Medicine, 06510 [Recruiting]
  • Saint Louis, Missouri, United States, Washington University School of Medicine, 63110 [Recruiting]
Last updated 2022-02-04