Clinical trial NCT01043640
Conditions: Mucopolysaccharidosis Hurler Syndrome Hunter Syndrome Maroteaux-Lamy Syndrome Sly Syndrome Alpha Mannosidosis Fucosidosis Aspartylglucosaminuria Adrenoleukodystrophy (ALD) Krabbe Disease Metachromatic Leukodystrophy (MLD) Sphingolipidoses Peroxisomal Disorders
Keywords: inherited metabolic disorders
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 2009-12-01; Completion date: 2017-06-01
Enrollment: 46 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
Primary Objective:

* 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

Secondary Objectives:

* 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.

Arms: arm 1: Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Interventions: intervention 1: Campath-1H intervention 2: Cyclophosphamide intervention 3: Busulfan intervention 4: Allogeneic stem cell transplantation intervention 5: Cyclosporine A intervention 6: Mycophenolate Mofetil
Intervention descriptions: intervention 1: Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV) intervention 2: Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily. intervention 3: 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 intervention 4: Administered \> 24 hours after last dose of busulfan. intervention 5: 2.5 mg/kg/dose intravenous (IV\_ beginning on day -3. Frequency of daily dosing will be based on the recipient's body weight:

* If body weight is ≤ 40 kg dosing will be 3 times daily
* If body weight is \> 40 kg dosing will be 2 times daily An attempt will be made to maintain a trough cyclosporine level of 250 mg/L to 350 mg/L. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CsA will be converted to an oral form at a dose 2 times the current IV dose (maximum 12.5 mg/kg/day as initial oral dose). intervention 6: 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.

Protocol documents: