Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
Rationale: Chemotherapy administration before a donor stem cell transplant is necessary to stop the patient's immune system from rejecting the donor's stem cells. When healthy stem cells from a donor are infused into the patient, the donor white blood cells can provide the missing enzyme that causes the metabolic disease. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. This may be an effective treatment for inherited metabolic disorders.
Purpose: The design of this study is to achieve donor cell engraftment in patients with standard-risk inherited metabolic diseases with limited peri-transplant morbidity and mortality. This will be achieved through the administration of the chemotherapy regimen described. The intention is to follow transplanted patient for years after transplant monitoring them for complications of their disease and assisting families with a multifaceted interdisciplinary approach.
Metachromatic Leukodystrophy (MLD)
Procedure: Allogeneic 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:||Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders|
- Number of Patients with Donor Derived Engraftment [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: No ]
- Number of Patients with Graft-Versus-Host Disease (GVHD) by Severity [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: No ]
- Number of Patients Died Peri-Transplant [ Time Frame: By Day 100 Post Transplant ] [ Designated as safety issue: Yes ]
- Donor Cell Chimerism Following Transplant [ Time Frame: Day 28, Day 42, Day 100, Month 6, Yearly Post Transplant ] [ Designated as safety issue: No ]
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||June 2017|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Transplant Patients
Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV)
Other Name: AlemtuzumabDrug: Cyclophosphamide
Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.
Other Name: Cytoxan(R)Drug: Busulfan
Administered every 6 hours: If < or = 12 kg then 1.1 mg/kg/dose intravenous (IV). If > 12 kg then 0.8 mg/kg/dose IV
Other Name: Busulfex(R)Procedure: Allogeneic stem cell transplantation
Administered > 24 hours after last dose of busulfan.
Other Name: stem cell transplantDrug: Cyclosporine A
2.5 mg/kg/dose intravenous (IV_ beginning on day -3. Frequency of daily dosing will be based on the recipient's body weight:
Other Name: CsADrug: Mycophenolate Mofetil
15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: The same dosage is used orally or intravenously. Stop MMF at day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Other Name: MMF
- To estimate the proportion of patients with donor derived engraftment at day 100 post transplant as defined by 80% or greater donor cells in the CD3 (T cell) fraction
- To determine the incidence and severity of graft-versus-host disease (GVHD) by day 100
- To determine the incidence of peri-transplant mortality (death by day 100)
- To monitor donor cell chimerism at various time points following allogeneic transplantation with this transplant regimen as determined at day 28, 42, 100, 6 months and yearly for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01043640
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Paul Orchard, MD||Masonic Cancer Center, University of Minnesota|