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

NCT ID: NCT02171104

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

149 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-07-10

Study Completion Date

2029-07-14

Brief Summary

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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).

Detailed Description

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Conditions

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IMD - Except Haplo-identical

Inherited Metabolic Disease (IMD) - Except Haplo-Identical

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

IMD Preparative Regimen

Intervention Type DRUG

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

OP - Except Haplo-Identical

Severe Osteoperosis (OP) - Except Haplo-Identical

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

Osteopetrosis Only Preparative Regimen

Intervention Type DRUG

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

OP and IMD -Haplo-Identical Only

Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD)

-Haplo-Identical Only

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

Osteopetrosis Haploidentical Only Preparative Regimen

Intervention Type DRUG

* Rituximab
* Alemtuzumab
* Busulfan
* Fludarabine

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

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

IMD Preparative Regimen

Intervention Type DRUG

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

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

Intervention Type DRUG

N-acetylcysteine start day +1 through day +28

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

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

IMD Preparative Regimen

Intervention Type DRUG

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

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

Intervention Type DRUG

N-acetylcysteine start day +1through day +56

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

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

IMD Preparative Regimen

Intervention Type DRUG

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

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

Intervention Type DRUG

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

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

See intervention descriptions.

Group Type EXPERIMENTAL

Stem Cell Transplantation

Intervention Type BIOLOGICAL

Infusion given on Day 0

IMD Preparative Regimen

Intervention Type DRUG

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

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

Intervention Type DRUG

N-acetylcysteine, celecoxib, vitamin E and alpha lipoic acid start day of admission (prior to conditioning regimen) and continue through day +100

Interventions

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Stem Cell Transplantation

Infusion given on Day 0

Intervention Type BIOLOGICAL

IMD Preparative Regimen

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

Intervention Type DRUG

Osteopetrosis Only Preparative Regimen

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

Intervention Type DRUG

Osteopetrosis Haploidentical Only Preparative Regimen

* Rituximab
* Alemtuzumab
* Busulfan
* Fludarabine

Intervention Type DRUG

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

N-acetylcysteine start day +1 through day +28

Intervention Type DRUG

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

N-acetylcysteine start day +1through day +56

Intervention Type 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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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)
Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Orchard, M.D.

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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2013LS104

Identifier Type: -

Identifier Source: org_study_id

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