Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism

University of Minnesota (UMN)

Status and phase

Terminated

Phase 2

Conditions

Sphingolipidoses

Wolman's Disease

Hurler's Syndrome

Sly Syndrome

Niemann-Pick Disease, Type C

Aspartylglucosaminuria

Maroteaux-Lamy Syndrome

Fucosidosis

Niemann-Pick Disease Type B

Krabbe Disease

Alpha Mannosidosis

Treatments

Drug: Campath-1H

Drug: Busulfan

Drug: Cyclophosphamide

Procedure: Stem Cell Transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT00668564

MT2008-02

0801M25202 (Other Identifier)

Details and patient eligibility

About

The primary objective of this clinical trial is to evaluate the ability to achieve and sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of metabolism undergoing hematopoietic stem cell transplantation (HCT).

Full description

This has been an ongoing area of interest by our group at the Univ. of Minnesota, but this is a new protocol to take the place of several older protocols. While survival has been very good on the prior protocols over the past decade, incomplete engraftment has remained somewhat problematic. Therefore, we have modified the preparative regimen somewhat to increase engraftment by replacing anti-thymocyte globulin (ATG) with Campath-1H, a drug that is more immune suppressive. In addition, we have modified the supportive care regimen. Based on this, we will monitor levels of an anti-oxidant therapy (N-acetylcysteine) and biomarkers of inflammation and oxidative stress for the families that consent to these research studies.

Enrollment

18 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Mucopolysaccharidosis (MPS) Disorders:
- MPS IH (Hurler syndrome)
- MPS-VI (Maroteaux-Lamy syndrome)
- MPS VII (Sly syndrome).
Glycoprotein metabolic disorders:
- Alpha mannosidosis
- Fucosidosis
- Aspartylglucosaminuria
Sphingolipidoses and Recessive Leukodystrophies: Presymptomatic patients with globoid cell leukodystrophy (GLD, also known as Krabbe disease) and metachromatic leukodystrophy (MLD) will be eligible for treatment on this protocol. White matter disease by magnetic resonance imaging (MRI) alone is not an exclusion if the patient is asymptomatic.
Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders associated with of very long chain fatty acids (VLCFA) elevation, identified by family history or laboratory testing (including neonatal screening), are eligible for this protocol. White matter disease by MRI alone is not an exclusion if the patient is asymptomatic.
Other Inherited Diseases of Metabolism:
- Wolman syndrome (acid lipase deficiency)
- Niemann-Pick B patients (sphingomyelin deficiency)
- Niemann-Pick C subtype 2
Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program: Priority will be as follows, although in circumstances in which timing is of the essence, cord blood grafts may be chosen over an unrelated graft, despite the priority listed above.
Multidisciplinary Evaluation: Patients will be eligible for transplantation only after they are seen and evaluated by members of the Inherited Metabolic and Storage Disease Program (IMSD) team, and the team has offered transplantation to the patient/family.

Exclusion criteria

Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be considered for other treatment protocols.
Major organ dysfunction. Evidence of major organ impairment, including:
- Cardiac: left ventricular ejection fraction <40%
- Renal: serum creatinine >2.5 x normal for age
- Hepatic: total bilirubin >3 x normal, or Alanine transaminase (ALT) > 3 x normal
- Pulmonary: requirement for continuous oxygen supplementation
Pregnancy
Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
Patients >21 years of age.