Bone marrow transplant for young patients with non-malignant disorders
A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders
This study is testing if a special type of bone marrow transplant is safe and effective for young people with serious non-cancerous blood disorders like sickle cell disease.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 29 (estimated) |
| Ages | 1 Day to 21 Years |
| Sex | All |
| Sponsor | Washington University School of Medicine Academic / other |
| Drugs / interventions | alemtuzumab, fludarabine |
| Locations | 4 sites (New Haven, Connecticut and 3 other locations) |
| Trial ID | NCT03128996 on ClinicalTrials.gov |
What this trial studies
This study evaluates the effectiveness and safety of familial HLA mismatched bone marrow transplants in patients under 21 years old with non-malignant disorders. Participants will undergo a reduced intensity conditioning regimen followed by the transplant procedure. The primary goal is to assess donor cell engraftment and safety at 100 days and one year after the transplant. The study focuses on patients with severe manifestations of conditions like sickle cell disease, bone marrow failure syndromes, and other metabolic or immunologic disorders.
Who should consider this trial
Good fit: Ideal candidates are patients under 21 years old with severe manifestations of non-malignant disorders requiring a bone marrow transplant.
Not a fit: Patients over 21 years old or those with malignant disorders will not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a safer and effective treatment option for young patients with severe non-malignant disorders.
How similar studies have performed: Other studies have shown promise with similar approaches in bone marrow transplantation for non-malignant disorders, indicating potential for success.
Eligibility criteria
Show full inclusion / exclusion 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)
Where this trial is running
New Haven, Connecticut and 3 other locations
- Yale School of Medicine — New Haven, Connecticut, United States (Recruiting)
- Nemours Children's Health — Wilmington, Delaware, United States (Recruiting)
- Helen DeVos Children's Hospital — Grand Rapids, Michigan, United States (Recruiting)
- Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Shalini Shenoy, MD — Washington University School of Medicine
- Study coordinator: Shalini Shenoy, MD
- Email: shalinishenoy@wustl.edu
- Phone: 314-454-6018
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.