Conditions: Lysosomal Storage Disease Peroxisomal Disorder
Keywords: bone marrow transplantation reduced intensity conditioning Adrenoleukodystrophy Metachromatic Leukodystrophy Globoid Cell Leukodystrophy Wolman's disease GM1 gangliosidosis Tay Sachs disease Sanfilippo syndrome Sandhoff disease inherited metabolic I-cell disease mucolipidosis II
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 3
Healthy volunteers: no

Brief summary:
This study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) in patients with high-risk lysosomal and peroxisomal disorders using a novel conditioning regimen for hematopoietic cell transplantation (HCT). After a reduced-intensity conditioning regimen using volumetric-modulated arc therapy (VMAT)-delivered low-dose total body irradiation (TBI) with highly conformal marrow boosting, patients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability.

Detailed description:
The conditioning regimen consists of alemtuzumab (Campath-1H), clofarabine, melphalan, and VMAT-delivered low-dose TBI with boosted marrow irradiation. Additional graft-versus-host disease prophylaxis consists of mycophenolate mofetil and cyclosporine.

Arms:
arm 1: Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m\^2 IV on days -9 through -5, melphalan 140 mg/m\^2 IV on day -4 and Total Body Irradiation with Marrow Boosting \[ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure\] by Volumetric-Modulated Arc Therapy \[VMAT\] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor.

Interventions: intervention 1: Campath-1H intervention 2: Clofarabine intervention 3: Melphalan intervention 4: Total Body Irradiation with Marrow Boosting intervention 5: Hematopoietic stem cell transplantation intervention 6: Cyclosporine A intervention 7: Mycophenolate mofetil
Intervention descriptions: intervention 1: A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8. intervention 2: A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,

-8, -7, -6, and -5. intervention 3: A single dose of 140 mg/m2 will be given IV on day -4 over 15 minutes. intervention 4: 1. Dose to total body 200 cGy in single dose
2. Dose to bone marrow of the following bones 800 cGy in 5 divided daily fractions (160 cGy x 5 doses ). Treated with up to 3 abutting VMAT photon arcs from top of head to maximum inferior border. intervention 5: Patients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability. intervention 6: Patients will receive CsA therapy beginning on day -3. Dosing of CsA will be 2.5 mg/kg/dose IV; if the recipient body weight is \<40 kg, dosing will be 3 times daily, and if \> 40 kg, twice daily. An attempt will be made to maintain a trough cyclosporine level of 200 mg/L to 400 mg/L. intervention 7: Patients will receive mycophenolate mofetil (MMF) therapy beginning on day -3. Dosing of MMF will be 1 gram three times daily (total daily dose 3 grams/day) if the recipient is \>50 kg, or 15 mg/kg/dose three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.

Protocol document: