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Active, Not Recruiting

NCT Number: NCT02171104

MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis

This single-institution, phase II study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) using busulfan- and fludarabine-based conditioning regimens with busulfan therapeutic drug monitoring (TDM) for patients with various inherited metabolic disorders (IMD) and severe osteopetrosis (OP).

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Mucopolysaccharidosis Disorders Abnormalities, Multiple Acyl-CoA Oxidase Deficiency Adrenoleukodystrophy With Cerebral Involvement Alpha-Mannosidosis Alpha-Methylacyl-CoA Racemase Deficiency Alpha-methylacyl-CoA Racmase Deficiency Aspartylglucosaminuria Bone Diseases Bone Diseases, Developmental Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Carbohydrate Metabolism, Inborn Errors Central Nervous System Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases D-Bifunctional Enzyme Deficiency Demyelinating Diseases Digestive System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Fucosidosis Genetic Diseases, Inborn Genetic Diseases, X-Linked Globoid Cell Leukodystrophy Glycoprotein Metabolic Disorders Hereditary Central Nervous System Demyelinating Diseases Hereditary Diffuse Leukoencephalopathy with Spheroids Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS; CSF1R Mutation) Heredodegenerative Disorders, Nervous System Hunter Syndrome Hurler Syndrome Infantile Refsum Disease Inherited Metabolic Disorders Intellectual Disability Kidney Diseases Leukodystrophy, Globoid Cell Leukodystrophy, Metachromatic Leukoencephalopathies Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Liver Diseases Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Male Urogenital Diseases Mannosidase Deficiency Diseases Maroteaux Lamy Syndrome Metabolic Diseases Metabolism, Inborn Errors Metachromatic Leukodystrophy Mitochondrial Neurogastrointestingal Encephalopathy Mucinoses Mucopolysaccharidoses Mucopolysaccharidosis I Mucopolysaccharidosis II Mucopolysaccharidosis VI Mucopolysaccharidosis VII Multifunctional Enzyme Deficiency Musculoskeletal Diseases Neonatal Adrenoleukodystrophy Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Niemann-Pick B Niemann-Pick C Subtype 2 Nutritional and Metabolic Diseases Osteochondrodysplasias Osteopetrosis Osteosclerosis Peroxisomal ACYL-COA oxidase deficiency Peroxisomal Disorders Pseudo-Zellweger syndrome Recessive Leukodystrophies Refsum Disease, Infantile Severe Osteopetrosis Skin and Connective Tissue Diseases Sly Syndrome Sphingolipidoses Sphingomyelin Deficiency Sulfatidosis Urogenital Diseases Urologic Diseases X-Linked Intellectual Disability Zellweger Syndrome

Age range

Up to 55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • 0 through 55 years of age
  • Adequate graft available
  • Adequate organ function
  • Eligible Diseases:
  • Mucopolysaccharidosis Disorders:
  • MPS IH (Hurler syndrome)
  • MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
  • MPS VI (Maroteaux-Lamy syndrome)
  • MPS VII (Sly syndrome)
  • Glycoprotein Metabolic Disorders:
  • Alpha mannosidosis
  • Fucosidosis
  • Aspartylglucosaminuria
  • Sphingolipidoses and Recessive Leukodystrophies:
  • Globoid cell leukodystrophy
  • Metachromatic leukodystrophy
  • Niemann-Pick B patients (sphingomyelin deficiency)
  • Niemann-Pick C subtype 2
  • Peroxisomal Disorders:
  • Adrenoleukodystrophy with cerebral involvement
  • Zellweger syndrome
  • Neonatal Adrenoleukodystrophy
  • Infantile Refsum disease
  • Acyl-CoA-Oxidase Deficiency
  • D-Bifunctional enzyme deficiency
  • Multifunctional enzyme deficiency
  • Alpha-methylacyl-CoA Racmase Deficiency (AMACRD)
  • Mitochondrial Neurogastrointestingal Encephalopathy (MNGIE)
  • Severe Osteopetrosis (OP)
  • Hereditary Leukoencephalopathy with axonal spheroids (HDLS; CSF1R mutation)
  • Other Inherited Metabolic Disorders (IMD): Patients will also be considered who have other life-threatening, rare lysosomal, peroxisomal or other similar inherited disorders characterized by white matter disease or other neurologic manifestations for which there is rationale that transplantation would be of benefit, such as certain patients with Wolman's disease, GM1 gangliosidosis, I-cell disease, Tay-Sachs disease, Sandhoff disease or others.
  • Voluntary written consent

Exclusion criteria

  • Pregnancy - menstruating females must have a negative serum or urine pregnancy test within 14 days of study treatment start
  • Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol (patients excluded for this reason may be eligible for other institutional protocols)
  • Uncontrolled bacterial, fungal or viral infections including HIV (including active infection with Aspergillus or other mold within 30 days)

Treatment and study plan

Stem Cell Transplantation

Biological

Infusion given on Day 0

IMD Preparative Regimen

Drug
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan

Osteopetrosis Only Preparative Regimen

Drug
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan
  • Thiotepa

Osteopetrosis Haploidentical Only Preparative Regimen

Drug
  • Rituximab
  • Alemtuzumab
  • Busulfan
  • Fludarabine

cALD SR-A (Standard-Risk, Regimen A)

Drug

N-acetylcysteine start day +1 through day +28

cALD SR-B (Standard-Risk, Regimen B)

Drug

N-acetylcysteine start day +1through day +56

cALD HR-D (High-Risk, Regimen C)

Drug

N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100

cALD HR-D (High-Risk, Regimen D)

Drug

N-acetylcysteine, celecoxib, vitamin E and alpha lipoic acid start day of admission (prior to conditioning regimen) and continue through day +100

Primary outcomes

  1. Percent of subjects who achieve high-level donor hematopoietic engraftment

    Time frame: Day +42 post-transplant

    Defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant

  2. Percent of subjects who achieve high-level donor hematopoietic engraftment

    Time frame: Day +100 post-transplant

    Defined as ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant

Secondary outcomes

  1. Graft-versus-host disease

    Time frame: Day +100 post-transplant

    Incidence and severity of GvHD

  2. Transplant-related mortality

    Time frame: Day +100 post-transplant

    Incidence of TRM

  3. Regimen-related toxicity

    Time frame: Day +100 post-transplant

    Defined as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease

  4. Post-HSCT changes in disease

    Time frame: 1 year

    Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis

  5. Post-HSCT changes in disease

    Time frame: 2 years

    Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis

Sponsors and collaborators

Lead sponsor

Masonic Cancer Center, University of Minnesota

Other

Registry information

Official study title

MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG

Important dates

Study start
2014
Primary completion
2026
Study completion
2029
First posted
Jun 23, 2014
Registry last updated
Jan 7, 2026

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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