A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders
Washington University School of Medicine
Summary
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.
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
- Age range
- 0–21 years
- Sex
- All
- Healthy volunteers
- No
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 q…
Interventions
- DrugRIC regimen
Days -60 to -21: hydroxyurea (30mg/kg/day po) \>6hrs prior to 1st dose: alemtuzumab (3mg IV) Day -21: alemtuzumab (10mg IV or S/C) Day -20: alemtuzumab (15mg IV or S/C) (10mg if \< 10kg) Day -19: alemtuzumab (20mg IV or S/C) (10mg if \< 10kg) Days -8 to -4: fludarabine (30mg/m2/day IV) Day -4: thiotepa (8mg/kg IV) Day -3: melphalan (140mg/m2) Days -2 to -1: rest days/no therapy Day 0: bone marrow transplant
- DrugGVHD prophylaxis regimen
Day +3 to +4: cyclophosphamide (50mg/kg/day IV) Day +5: Start of tacrolimus \& Start of mycophenolate mofetil (MMF) Days +5, +14, +30, +60, +90: abatacept (IND) (10mg/kg/day IV) Day +90: rituximab (375mg/m2 IV once) Patients \>/= 12 yrs - Days +120 to +180: abatacept (IND) monthly (10mg/kg/day IV) Patients \>/= 12 yrs - Days +210 to +390: abatacept (IND) monthly (5mg/kg/day) Patients \<12 yrs - Days +120 to +390: abatacept (IND) monthly (5mg/kg/day IV)
Locations (4)
- Yale School of MedicineNew Haven, Connecticut
- Nemours Children's HealthWilmington, Delaware
- Helen DeVos Children's HospitalGrand Rapids, Michigan
- Washington University School of MedicineSt Louis, Missouri