Reduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · Apr 20, 2017

Keywords

ClinConnect Summary

This clinical trial is investigating a type of bone marrow transplant called familial HLA-mismatched bone marrow transplant for young patients under 21 years old who have serious non-cancer-related health conditions, such as severe sickle cell disease, bone marrow failure syndromes, and certain metabolic and immunologic disorders. The goal is to see how effective and safe this transplant method is for these patients, who may not have a fully matched donor available. To be eligible, participants need to have specific severe symptoms related to their condition and meet certain health criteria.

If your child qualifies and decides to participate, they will receive a transplant from a family member who is not an exact match. Throughout the study, the medical team will closely monitor your child for any side effects and how well the treatment is working. It’s important to know that participants must agree to certain health checks and follow guidelines regarding contraception if they are of childbearing age. The trial is currently recruiting, and families interested in this option can reach out to learn more about participation.

Gender

ALL

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
• • 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.
• 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)