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NCT Number: NCT01043640

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.

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Key information

Conditions

Mucopolysaccharidosis Adrenal Gland Diseases Adrenal Insufficiency Adrenoleukodystrophy Adrenoleukodystrophy (ALD) Alpha Mannosidosis Aspartylglucosaminuria Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Carbohydrate Metabolism, Inborn Errors Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Demyelinating Diseases Endocrine System Diseases Fucosidosis Genetic Diseases, Inborn Genetic Diseases, X-Linked Hereditary Central Nervous System Demyelinating Diseases Heredodegenerative Disorders, Nervous System Hunter Syndrome Hurler Syndrome Intellectual Disability Krabbe Disease Leukodystrophy, Globoid Cell Leukodystrophy, Metachromatic Leukoencephalopathies Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Mannosidase Deficiency Diseases Maroteaux-Lamy Syndrome Metabolic Diseases Metabolism, Inborn Errors Metachromatic Leukodystrophy (MLD) Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis I Mucopolysaccharidosis II Mucopolysaccharidosis VI Mucopolysaccharidosis VII Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Nutritional and Metabolic Diseases Peroxisomal Disorders Skin and Connective Tissue Diseases Sly Syndrome Sphingolipidoses Sulfatidosis X-Linked Intellectual Disability alpha-Mannosidosis

Age range

Up to 21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Must have diagnosis of one of the following: mucopolysaccharidosis disorder, glycoprotein metabolic disorder, sphingolipidoses or inherited leukodystrophy, peroxisomal disorder or other inherited diseases of metabolism
  • Must have an acceptable graft source as defined by University of Minnesota criteria
  • Adequate organ function

Exclusion criteria

  • Pregnant - menstruating females must have a negative serum pregnancy test within 14 days of treatment start
  • Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology

Treatment and study plan

Campath-1H

Drug

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

Other names: Alemtuzumab

Cyclophosphamide

Drug

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

Other names: Cytoxan(R)

busulfan

Drug

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 names: Busulfex(R)

allogeneic stem cell transplantation

Procedure

Administered > 24 hours after last dose of busulfan.

Other names: stem cell transplant

Cyclosporine A

Drug

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).

Other names: CsA

Mycophenolate mofetil

Drug

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 names: MMF

Primary outcomes

  1. Number of Patients With Donor Derived Engraftment

    Time frame: Day 100 Post Transplant

    Donor derived engraftment is defined as 80 percent or greater donor cells in the recipient's bone marrow and blood cells.

Secondary outcomes

  1. Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)

    Time frame: Day 100 Post Transplant

    GVHD grading is performed using modified Glucksberg criteria and is as follows:

    grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

  2. Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)

    Time frame: Day 100 Post Transplant

    GVHD grading is performed using modified Glucksberg criteria and is as follows:

    grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

  3. Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)

    Time frame: Day 100 Post Transplant

    GVHD grading is performed using modified Glucksberg criteria and is as follows:

    grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

  4. Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)

    Time frame: Day 100 Post Transplant

    GVHD grading is performed using modified Glucksberg criteria and is as follows:

    grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

  5. Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)

    Time frame: Day 100 Post Transplant

    GVHD grading is performed using modified Glucksberg criteria and is as follows:

    grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

  6. Number of Patients Who Died Peri-Transplant

    Time frame: By Day 100 Post Transplant

    Peri-transplant is defined as within 100 days of transplant.

  7. Donor Cell Chimerism Following Transplant

    Time frame: Day 28

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

  8. Donor Cell Chimerism Following Transplant

    Time frame: Day 42

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

  9. Donor Cell Chimerism Following Transplant

    Time frame: Day 100

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

  10. Donor Cell Chimerism Following Transplant

    Time frame: 6 months

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

  11. Donor Cell Chimerism Following Transplant

    Time frame: One year

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

Sponsors and collaborators

Lead sponsor

Masonic Cancer Center, University of Minnesota

Other

Registry information

Official study title

Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders

Important dates

Study start
2009
Primary completion
2015
Study completion
2017
First posted
Jan 7, 2010
Registry last updated
Feb 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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