Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

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.

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

Interventions

DRUG

Campath-1H

Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV)

DRUG

Cyclophosphamide

Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.

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

PROCEDURE

Allogeneic stem cell transplantation

Administered \> 24 hours after last dose of busulfan.

DRUG

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: * 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).

DRUG

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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Paul Orchard, MD · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-12-31

Primary Completion

2015-06-30

Completion

2017-06-30

Countries

• United States

Study Locations