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

study id #: NCT02171104

condition: 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

status: Recruiting

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).

intervention: Stem Cell Transplantation, IMD Preparative Regimen, Osteopetrosis Only Preparative Regimen, Osteopetrosis Haploidentical Only Preparative Regimen, cALD SR-A (Standard-Risk, Regimen A), cALD SR-B (Standard-Risk, Regimen B), cALD HR-D (High-Risk, Regimen C), cALD HR-D (High-Risk, Regimen D)

results: https://clinicaltrials.gov/ct2/show/results/NCT02171104

last updated: February 26, 2022

start date: July 10, 2014

estimated completion: December 2022

last updated: November 5, 2021

phase of development: Phase 2

size / enrollment: 100

primary outcomes:

• 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
  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 outcomes:

• Graft-versus-host disease
  Day +100 post-transplant
• Transplant-related mortality
  Day +100 post-transplant
• Regimen-related toxicity
  Day +100 post-transplant
• Post-HSCT changes in disease
  1 year
• Post-HSCT changes in disease
  2 years

inclusion 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: 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)

sponsor: Masonic Cancer Center, University of Minnesota

contacts: Lisa Burke, 612-273-8482, [email protected]

investigators: Paul Orchard, M.D.,Masonic Cancer Center, University Of Minnesota

trial center locations: United States

• United States, Minnesota
  Masonic Cancer Center, University of Minnesota
  Lisa Burke, 612-273-8482, [email protected]