This single-institution, phase II study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) using busulfan- and fludarabine-based conditioning regimens with busulfan therapeutic drug monitoring (TDM) for patients with various inherited metabolic disorders (IMD) and severe osteopetrosis (OP).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
149
Infusion given on Day 0
* Anti-thymocyte Globulin (ATG) * Fludarabine * Busulfan
* Anti-thymocyte Globulin (ATG) * Fludarabine * Busulfan * Thiotepa
* Rituximab * Alemtuzumab * Busulfan * Fludarabine
N-acetylcysteine start day +1 through day +28
N-acetylcysteine start day +1through day +56
N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100
N-acetylcysteine, celecoxib, vitamin E and alpha lipoic acid start day of admission (prior to conditioning regimen) and continue through day +100
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Percent of subjects who achieve high-level donor hematopoietic engraftment
Defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant
Time frame: Day +42 post-transplant
Percent of subjects who achieve high-level donor hematopoietic engraftment
Defined as ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant
Time frame: Day +100 post-transplant
Graft-versus-host disease
Incidence and severity of GvHD
Time frame: Day +100 post-transplant
Transplant-related mortality
Incidence of TRM
Time frame: Day +100 post-transplant
Regimen-related toxicity
Defined as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease
Time frame: Day +100 post-transplant
Post-HSCT changes in disease
Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Time frame: 1 year
Post-HSCT changes in disease
Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Time frame: 2 years
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