This is a phase II trial of T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation in patients with inherited bone marrow failure (BMF) disorders to eliminate the need for routine graft-versus-host disease (GVHD) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
300 cGy with thymic shielding on day -6
10 mg/kg IV daily on days -5, -4, -3, and -2
35 mg/m2 IV daily on days -5, -4, -3, and -2
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
Initiate G-CSF 5mcg/kg per day IV on day +1 (continue until ANC \>2.5 x 10\^9/L for 3 consecutive days or single day ANC \>3000 Arm 1 and Arm 3)
5 mg/kg IV daily on days -5, -4, -3, and -2
200 mg/m2 IV once on day -1
Busulfan 0.6 mg/kg if \> 4 years old and/or \>12 kg (0.8 mg/kg IV if ≤ 4 years old and/or ≤ 12 kg) is given IV over 2 hours every 12 hours for 2 days.
Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
If available, MEL dosing will be model-based using Bayesian methodology. If Bayesian methodology is unavailable, MEL dosing will be weight-based: MEL 70 mg/m2 for patients ≥10 kg (2.35 mg/kg for patients \<10 kg\^) IV for one dose over 30 minutes.
Rituximab will be given once on treatment plans 1-3 on day -1.
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGGrade II-IV acute graft versus host disease (GVHD)
incidence of grade II-IV acute graft versus host disease (GVHD)
Time frame: Day 100
Neutrophil engraftment
Rate of neutrophil engraftment (defined as the first of three consecutive days after HCT that the patient's absolute neutrophil counts is ≥ 0.5x109 per liter)
Time frame: Day 42
Platelet engraftment
Time to platelet engraftment (First of three consecutive days after HCT that the patient's platelet count ≥ 20x10\^9 per liter)
Time frame: Day 42
Acute graft versus host disease (aGVHD)
Incidence of grade III-IV acute graft versus host disease
Time frame: Day 100
Chronic graft versus host disease (cGVHD)
Incidence of chronic graft versus host disease after transplant
Time frame: 1 Year after transplant
Regimen related toxicity
Incidence of regimen related toxicity based on CTCAE v5
Time frame: 30 Days after transplant
Bacterial, viral and fungal infections
Incidence of bacterial, viral and fungal infections
Time frame: 1 Year after transplant
Opportunistic infections
Incidence of opportunistic infections
Time frame: 100 Days after transplant
Overall survival (OS)
Incidence of overall survival
Time frame: 1 Year after transplant
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