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

Hunter Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02171104
• Other study ID #: 2013LS104
• Status: Recruiting
• Phase: Phase 2
• Start date: July 10, 2014
• Est. completion date: July 14, 2028

Study information

• Verified date: November 2023
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Lisa Burke
• Phone: 612-273-8482
• Email: lburke3[@]Fairview.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 14, 2028
• Est. primary completion date: July 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acyl-CoA Oxidase Deficiency
• Adrenoleukodystrophy
• Adrenoleukodystrophy With Cerebral Involvement
• Alpha-Mannosidosis
• Alpha-methylacyl-CoA Racmase Deficiency
• Aspartylglucosaminuria
• Brain Diseases
• D-Bifunctional Enzyme Deficiency
• Fucosidosis
• Globoid Cell Leukodystrophy
• Glycoprotein Metabolic Disorders
• Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS; CSF1R Mutation)
• Hunter Syndrome
• Hurler Syndrome
• Infantile Refsum Disease
• Inherited Metabolic Disorders
• Leukodystrophy, Globoid Cell
• Leukodystrophy, Metachromatic
• Leukoencephalopathies
• Maroteaux Lamy Syndrome
• Metabolic Diseases
• Metachromatic Leukodystrophy
• Mitochondrial Neurogastrointestingal Encephalopathy
• Mucopolysaccharidoses
• Mucopolysaccharidosis Disorders
• Mucopolysaccharidosis I
• Mucopolysaccharidosis II
• Mucopolysaccharidosis VI
• Mucopolysaccharidosis VII
• Multifunctional Enzyme Deficiency
• Neonatal Adrenoleukodystrophy
• Niemann-Pick B
• Niemann-Pick C Subtype 2
• Osteopetrosis
• Peroxisomal Disorders
• Recessive Leukodystrophies
• Refsum Disease
• Severe Osteopetrosis
• Sly Syndrome
• Sphingolipidoses
• Sphingomyelin Deficiency
• Syndrome
• Zellweger Syndrome

Intervention

Biological:
• Stem Cell Transplantation
Infusion given on Day 0

Drug:
• IMD Preparative Regimen
Anti-thymocyte Globulin (ATG) Fludarabine Busulfan
• Osteopetrosis Only Preparative Regimen
Anti-thymocyte Globulin (ATG) Fludarabine Busulfan Thiotepa
• Osteopetrosis Haploidentical Only Preparative Regimen
Rituximab Alemtuzumab Busulfan Fludarabine
• cALD SR-A (Standard-Risk, Regimen A)
N-acetylcysteine start day +1 through day +28
• cALD SR-B (Standard-Risk, Regimen B)
N-acetylcysteine start day +1through day +56
• cALD HR-D (High-Risk, Regimen C)
N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100
• 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

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent 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	Day +42 post-transplant
Primary	Percent of subjects who achieve high-level donor hematopoietic engraftment	Defined as = 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant	Day +100 post-transplant
Secondary	Graft-versus-host disease	Incidence and severity of GvHD	Day +100 post-transplant
Secondary	Transplant-related mortality	Incidence of TRM	Day +100 post-transplant
Secondary	Regimen-related toxicity	Defined as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease	Day +100 post-transplant
Secondary	Post-HSCT changes in disease	Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis	1 year
Secondary	Post-HSCT changes in disease	Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis	2 years