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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2017 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT02171104
First received: June 20, 2014
Last updated: February 17, 2017
Last verified: February 2017
  Purpose
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 Intervention 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
Inherited Metabolic Disorders
Biological: Stem Cell Transplantation
Drug: IMD Preparative Regimen
Drug: Osteopetrosis Only Preparative Regimen
Drug: Osteopetrosis Haploidentical Only Preparative Regimen
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • percentage of subjects who achieve high-level donor hematopoietic engraftment (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) [ Time Frame: neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant ]

Secondary Outcome Measures:
  • percentage of subjects who develop graft-versus-host disease [ Time Frame: by Day +100 post-transplant ]
  • number of subjects who die from transplant complications [ Time Frame: Day +100 days post-transplant ]
  • incidence of regimen-related toxicity (such as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease) [ Time Frame: Day +100 post-transplant ]
  • incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical changes [ Time Frame: at 6 months, 1 year and yearly for a total of 5 years ]

Estimated Enrollment: 100
Actual Study Start Date: July 10, 2014
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inherited Metabolic Disease (IMD)
See intervention descriptions.
Biological: Stem Cell Transplantation
Infusion given on Day 0
Drug: IMD Preparative Regimen
  • Anti-thymocyte Globulin (ATG)
  • Fludarabine
  • Busulfan
Experimental: Severe Osteopetrosis (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: Severe Osteopetrosis (OP) -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

  Eligibility

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:

    1. Mucopolysaccharidosis Disorders ("IMD"):

      1. MPS IH (Hurler syndrome)
      2. MPS II (Hunter syndrome) if the patient has no or minimal evidence of symptomatic neurologic disease but is expected to have a neurologic phenotype
      3. MPS VI (Maroteaux-Lamy syndrome)
      4. MPS VII (Sly syndrome)
    2. Glycoprotein Metabolic Disorders ("IMD"):

      1. Alpha mannosidosis
      2. Fucosidosis
      3. Aspartylglucosaminuria
    3. Sphingolipidoses and Recessive Leukodystrophies ("IMD"):

      1. Globoid cell leukodystrophy
      2. Metachromatic leukodystrophy
      3. Niemann-Pick B patients (sphingomyelin deficiency)
      4. Niemann-Pick C subtype 2
    4. Peroxisomal Disorders ("IMD"):

      1. Adrenoleukodystrophy with cerebral involvement
      2. Zellweger syndrome
      3. Neonatal Adrenoleukodystrophy
      4. Infantile Refsum disease
      5. Acyl-CoA-Oxidase Deficiency
      6. D-Bifunctional enzyme deficiency
      7. Multifunctional enzyme deficiency
      8. Alpha-methylacyl-CoA Racmase Deficiency (AMACRD)
      9. Mitochondrial Neurogastrointestingal Encephalopathy (MNGIE)
    5. Severe Osteopetrosis (OP)
    6. Hereditary Leukoencephalopathy with axonal spheroids (HDLS; CSF1R mutation)
    7. Other Inherited Metabolic Disorders (IMD): Patients will also be considered who have other lifethreatening, 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.

Exclusion Criteria:

  • Any patient who in the judgment of the University of Minnesota Inherited Metabolic and Storage Disease Group has disease that is not likely to benefit from allogeneic HSCT, based on its nature, severity or state of progression
  • Prior myeloablative chemotherapy exposure within 4 months of the start of conditioning on this protocol
  • Uncontrolled bacterial, fungal or viral infections including HIV
  • Pregnancy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02171104

Contacts
Contact: Kim Nelson 612-273-2925 knelso62@fairview.org

Locations
United States, Minnesota
University of Minnesota Medical Center, Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Kim Nelson    612-273-2925    knelso62@fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Weston Miller, MD Masonic Cancer Center, University of Minnesota
  More Information

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02171104     History of Changes
Other Study ID Numbers: 2013LS104
Study First Received: June 20, 2014
Last Updated: February 17, 2017

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:
Disease
Syndrome
Brain Diseases
Mucopolysaccharidoses
Leukodystrophy, Globoid Cell
Sphingolipidoses
Mucopolysaccharidosis VI
Osteopetrosis
Mucopolysaccharidosis I
Mannosidase Deficiency Diseases
alpha-Mannosidosis
Mucopolysaccharidosis II
Adrenoleukodystrophy
Leukodystrophy, Metachromatic
Leukoencephalopathies
Metabolic Diseases
Peroxisomal Disorders
Aspartylglucosaminuria
Zellweger Syndrome
Refsum Disease, Infantile
Refsum Disease
Fucosidosis
Mucopolysaccharidosis VII
Intestinal Pseudo-Obstruction
Mitochondrial Encephalomyopathies
Hearing Loss, Sensorineural
Gonadal Dysgenesis, 46,XX
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on March 22, 2017