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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02171104
Recruitment Status : Recruiting
First Posted : June 23, 2014
Last Update Posted : November 3, 2022
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Disorders Hurler Syndrome Hunter Syndrome Maroteaux Lamy Syndrome Sly Syndrome Alpha-Mannosidosis Fucosidosis Aspartylglucosaminuria Glycoprotein Metabolic Disorders Sphingolipidoses Recessive Leukodystrophies Globoid Cell Leukodystrophy Metachromatic Leukodystrophy Niemann-Pick B Niemann-Pick C Subtype 2 Sphingomyelin Deficiency 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 Mitochondrial Neurogastrointestingal Encephalopathy Severe Osteopetrosis Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS; CSF1R Mutation) Inherited Metabolic Disorders Biological: Stem Cell Transplantation Drug: IMD Preparative Regimen Drug: Osteopetrosis Only Preparative Regimen Drug: Osteopetrosis Haploidentical Only Preparative Regimen Drug: cALD SR-A (Standard-Risk, Regimen A) Drug: cALD SR-B (Standard-Risk, Regimen B) Drug: cALD HR-D (High-Risk, Regimen C) Drug: cALD HR-D (High-Risk, Regimen D) Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
Actual Study Start Date : July 10, 2014
Estimated Primary Completion Date : July 14, 2025
Estimated Study Completion Date : July 14, 2028

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Mucopolysaccharidosis X-linked Adrenoleukodystrophy Adrenomyeloneuropathy Mucopolysaccharidosis Type II Leukodystrophy Metachromatic Leukodystrophy Krabbe Disease Mucopolysaccharidosis Type VI Mucopolysaccharidosis Type VII Hurler Syndrome Alpha-mannosidosis Sphingolipidosis Osteopetrosis Zellweger Syndrome Aspartylglycosaminuria Refsum Disease Peroxisomal Biogenesis Disorders Mitochondrial Neurogastrointestinal Encephalopathy Syndrome Fucosidosis Refsum Disease, Infantile Form D-bifunctional Protein Deficiency Neonatal Adrenoleukodystrophy Pseudoneonatal Adrenoleukodystrophy Mucopolysaccharidosis Type I Mucopolysaccharidosis Type IV Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsies Roussy Levy Syndrome

Arms and Interventions
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Arm Intervention/treatment
Experimental: IMD - Except Haplo-identical

Inherited Metabolic Disease (IMD) - Except Haplo-Identical

See intervention descriptions.

 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: IMD Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan
Experimental: OP - Except Haplo-Identical

Severe Osteoperosis (OP) - Except Haplo-Identical

See intervention descriptions.

 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: Osteopetrosis Only Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan
  • Thiotepa
Experimental: OP and IMD -Haplo-Identical Only

Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD)

-Haplo-Identical Only

See intervention descriptions.

 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: Osteopetrosis Haploidentical Only Preparative Regimen
  • Rituximab
  • Alemtuzumab
  • Busulfan
  • Fludarabine
Experimental: cALD SR-A (Standard-Risk, Regimen A)
See intervention descriptions.
 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: IMD Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan

Drug: cALD SR-A (Standard-Risk, Regimen A)
N-acetylcysteine start day +1 through day +28
Experimental: cALD SR-B (Standard-Risk, Regimen B)
See intervention descriptions.
 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: IMD Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan

Drug: cALD SR-B (Standard-Risk, Regimen B)
N-acetylcysteine start day +1through day +56
Experimental: cALD HR-C (High-Risk, Regimen C)
See intervention descriptions.
 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: IMD Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan

Drug: cALD HR-D (High-Risk, Regimen C)
N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100
Experimental: cALD HR-D (High-Risk, Regimen D)
See intervention descriptions.
 Biological: Stem Cell Transplantation
Infusion given on Day 0

Drug: IMD Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan

Drug: cALD HR-D (High-Risk, Regimen D)
N-acetylcysteine, celecoxib, vitamin E and alpha lipoic acid start day of admission (prior to conditioning regimen) and continue through day +100


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02171104


Contacts
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Contact: Lisa Burke 612-273-8482 lburke3@Fairview.org
Contact: Troy Lund, M.D.Ph.D. 612-625-4185 lundx072@umn.edu

Locations
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United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Lisa Burke    612-273-8482    lburke3@Fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Paul Orchard, M.D. Masonic Cancer Center, University of Minnesota
More Information
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02171104    
Other Study ID Numbers: 2013LS104
First Posted: June 23, 2014    Key Record Dates
Last Update Posted: November 3, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
allogeneic hematopoietic cell transplantation
bone marrow transplantation
IMD
AMACRD
 MNGIE
HDLS
OP
ALD
Additional relevant MeSH terms:
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Adrenoleukodystrophy
Osteopetrosis
Zellweger Syndrome
Brain Diseases
Mucopolysaccharidosis II
Leukoencephalopathies
Leukodystrophy, Metachromatic
Leukodystrophy, Globoid Cell
Sphingolipidoses
Fucosidosis
Refsum Disease
Refsum Disease, Infantile
Mucopolysaccharidoses
Mannosidase Deficiency Diseases
alpha-Mannosidosis
 Mucopolysaccharidosis I
Mucopolysaccharidosis VI
Peroxisomal Disorders
Mucopolysaccharidosis VII
Aspartylglucosaminuria
Metabolic Diseases
Disease
Syndrome
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases