Clinical trial NCT02171104: MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Official title: MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
Keywords: allogeneic hematopoietic cell transplantation
bone marrow transplantation
IMD
AMACRD
MNGIE
HDLS
OP
ALD
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2014-06-23
Enrollment: 100
Sex: ALL
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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)

Primary outcomes:
measure: Percent of subjects who achieve high-level donor hematopoietic engraftment
timeFrame: Day +42 post-transplant
measure: Percent of subjects who achieve high-level donor hematopoietic engraftment
timeFrame: Day +100 post-transplant
Secondary outcomes:
measure: Graft-versus-host disease
timeFrame: Day +100 post-transplant
measure: Transplant-related mortality
timeFrame: Day +100 post-transplant
measure: Regimen-related toxicity
timeFrame: Day +100 post-transplant
measure: Post-HSCT changes in disease
timeFrame: 1 year
measure: Post-HSCT changes in disease
timeFrame: 2 years
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Paul Orchard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: