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

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).

Conditions

• Infantile Refsum Disease
• 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
• 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

Interventions

BIOLOGICAL

Stem Cell Transplantation

Infusion given on Day 0

DRUG

IMD Preparative Regimen

* Anti-thymocyte Globulin (ATG) * Fludarabine * Busulfan

DRUG

Osteopetrosis Only Preparative Regimen

* Anti-thymocyte Globulin (ATG) * Fludarabine * Busulfan * Thiotepa

DRUG

Osteopetrosis Haploidentical Only Preparative Regimen

* Rituximab * Alemtuzumab * Busulfan * Fludarabine

DRUG

cALD SR-A (Standard-Risk, Regimen A)

N-acetylcysteine start day +1 through day +28

DRUG

cALD SR-B (Standard-Risk, Regimen B)

N-acetylcysteine start day +1through day +56

DRUG

cALD HR-D (High-Risk, Regimen C)

N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100

DRUG

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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Paul Orchard, M.D. · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-07-10

Primary Completion

2026-01-05

Completion

2029-07-14

FDA Drug

Yes

Countries

• United States

Study Locations