Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders
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.
Lysosomal Storage Disease
Radiation: Total Body Irradiation with Marrow Boosting
Biological: Hematopoietic stem cell transplantation
Drug: Cyclosporine A
Drug: Mycophenolate mofetil
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Donor (Allogeneic) Hematopoietic Engraftment [ Time Frame: Day 100 Following Hematopoietic Cell Transplant (HCT) ] [ Designated as safety issue: No ]Number of patients who achieve hematopoietic engraftment - assessment of nucleated peripheral blood cells for donor (allogeneic) chimerism following this reduced-intensity HCT.
- Transplant-Related Mortality [ Time Frame: Day 100 following HCT ] [ Designated as safety issue: Yes ]Incidence of death due to complications of HCT following this reduced-intensity conditioning regimen.
- Neurologic Outcomes [ Time Frame: Changes from Baseline, Days 30, 60, 100, Year 1, Year 2, Year 3 Following HCT ] [ Designated as safety issue: No ]Depending upon underlying primary disease, a combination of evaluative tools (e.g. brain magnetic resonance imaging (MRI), clinical neurologic exam, neuropsychologic testing, electromyography) will be applied for assessment of neurologic function and how it may be affected by this reduced-intensity HCT regimen.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||June 2020|
|Estimated Primary Completion Date:||June 2020 (Final data collection date for primary outcome measure)|
Experimental: Intent-To-Treat Patients
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.
A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.
Other Name: alemtuzumabDrug: Clofarabine
A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,
-8, -7, -6, and -5.
A single dose of 140 mg/m2 will be given IV on day -4 over 15 minutes.Radiation: Total Body Irradiation with Marrow Boosting
Other Name: Volumetric-Modulated Arc Therapy (VMAT)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.
Other Name: CsADrug: 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.
Other Name: MMF
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.
|Contact: Weston Miller, MDfirstname.lastname@example.org|
|Contact: Patricia Kleinke, RNemail@example.com|
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Weston Miller, MD 612-626-2778 firstname.lastname@example.org|
|Principal Investigator: Weston Miller, MD|
|Principal Investigator:||Weston Miller, MD||Masonic Cancer Center, University of Minnesota|