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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
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
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)
Yale School of Medicine
New Haven, Connecticut, United States
RECRUITINGNemours Children's Health
Wilmington, Delaware, United States
RECRUITINGHelen DeVos Children's Hospital
Grand Rapids, Michigan, United States
RECRUITINGWashington University School of Medicine
St Louis, Missouri, United States
RECRUITINGDonor engraftment
as measured by chimerism
Time frame: 100 days and 1 year post-transplant
Time to neutrophil engraftment
as measured by complete blood counts
Time frame: 100 days post-transplant
Time to platelet engraftment
as measured by complete blood counts
Time frame: 100 days post-transplant
Effect of BMT on pulmonary function
as measured by pulmonary function tests
Time frame: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on hepatic function
as measured by laboratory evaluations
Time frame: 90 days, 180 days, 1 year, and 2 years post-transplant
Effect of BMT on neurologic function
as measured by cognitive testing and quality of life surveys
Time frame: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on cardiac function
as measured by echocardiograms
Time frame: 90 days, 1 year, and 2 years post-transplant
Effect of BMT on renal function
as measured by laboratory evaluations
Time frame: 90 days, 180 days, 1 year, and 2 years post-transplant
Pharmacokinetics of alemtuzumab
as measured by maximum plasma concentration of alemtuzumab
Time frame: days -19, day 0, day +15, and day +30
Pharmacokinetics of abatacept
as measured by maximum plasma concentration of abatacept
Time frame: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
Incidence of acute graft-versus-host disease (GVHD)
as measured by protocol grading scale
Time frame: 1 year post-transplant
Incidence of chronic graft-versus-host disease (GVHD)
as measured by protocol grading scale
Time frame: 2 years post-transplant
Immune reconstitution
as measured by research laboratory evaluations
Time frame: days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant
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