NCT01626092

Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders

Treatment of High Risk, Inherited Lysosomal and Peroxisomal Disorders by Reduced-Intensity Hematopoietic Cell Transplantation and Low-Dose Total Body Irradiation With Marrow Boosting by Volumetric-Modulated Arc Therapy (VMAT)

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 55 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Lysosomal Storage Disease
• Peroxisomal Disorder

Interventions

Type	Name	Description
DRUG	Campath-1H	A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.
DRUG	Clofarabine	A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9, -8, -7, -6, and -5.
DRUG	Melphalan	A single dose of 140 mg/m2 will be given IV on day -4 over 15 minutes.
RADIATION	Total Body Irradiation with Marrow Boosting	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.
BIOLOGICAL	Hematopoietic stem cell transplantation	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.
DRUG	Cyclosporine A	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.
DRUG	Mycophenolate mofetil	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.

Timeline

• Start date: 2012-07-11
• Primary completion: 2013-11-01
• Completion: 2013-11-01
• First posted: 2012-06-22
• Last updated: 2017-12-05
• Results posted: 2016-10-11

Locations

1 site across 1 country: United States