Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
MT2017-17:T Cell Receptor Alpha/Beta T Cell Depleted Hematopoietic Cell Transplantation in Patients With Inherited Bone Marrow Failure (BMF) Disorders
About This Trial
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.
Who May Be Eligible (Plain English)
Original Eligibility Criteria
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Treatments Being Tested
Total Body Irradiation (TBI) (Plan 1)
300 cGy with thymic shielding on day -6
Cyclophosphamide (CY) (Plan 1)
10 mg/kg IV daily on days -5, -4, -3, and -2
Fludarabine (FLU)
35 mg/m2 IV daily on days -5, -4, -3, and -2
Methylprednisolone (MP)
1 mg/kg IV q12h on days -5, -4, -3, -2, and -1
Donor mobilized PBSC infusion
T cell receptor alpha/beta depletion (α/β TCD) peripheral blood stem cell (PBSC) transplantation on day 0
G-CSF
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)
Cyclophosphamide (CY) (Plan 2)
5 mg/kg IV daily on days -5, -4, -3, and -2
Rituximab
200 mg/m2 IV once on day -1
Busulfan
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
Alemtuzumab 0.2 mg/kg is given IV over 2 hours daily for 5 days (total dose 1 mg/kg)
Melphalan
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
Rituximab will be given once on treatment plans 1-3 on day -1.