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

University of Minnesota (UMN)

Status and phase: Active, not recruiting; Phase 2

Conditions: Neonatal Adrenoleukodystrophy; Hunter Syndrome; Zellweger Syndrome; Sly Syndrome; Severe Osteopetrosis; Aspartylglucosaminuria; Hereditary Leukoencephalopathy With Axonal Spheroids (HDLS; CSF1R Mutation); Metachromatic Leukodystrophy; D-Bifunctional Enzyme Deficiency; Alpha-methylacyl-CoA Racmase Deficiency; Maroteaux Lamy Syndrome; Niemann-Pick C Subtype 2; Infantile Refsum Disease; Sphingolipidoses; Peroxisomal Disorders; Acyl-CoA Oxidase Deficiency; Inherited Metabolic Disorders; Recessive Leukodystrophies; Hurler Syndrome; Multifunctional Enzyme Deficiency; Niemann-Pick B; Globoid Cell Leukodystrophy; Mucopolysaccharidosis Disorders; Glycoprotein Metabolic Disorders; Mitochondrial Neurogastrointestingal Encephalopathy; Sphingomyelin Deficiency; Alpha-Mannosidosis; Adrenoleukodystrophy With Cerebral Involvement; Fucosidosis

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02171104

2013LS104

Details and patient eligibility

About

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).

Enrollment: 149 patients

Sex: All

Ages: Under 55 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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149 participants in 7 patient groups

IMD - Except Haplo-identical

Experimental group

Description:

Inherited Metabolic Disease (IMD) - Except Haplo-Identical See intervention descriptions.

Treatment:

Drug: IMD Preparative Regimen

Biological: Stem Cell Transplantation

OP - Except Haplo-Identical

Experimental group

Description:

Severe Osteoperosis (OP) - Except Haplo-Identical See intervention descriptions.

Treatment:

Drug: Osteopetrosis Only Preparative Regimen

Biological: Stem Cell Transplantation

OP and IMD -Haplo-Identical Only

Experimental group

Description:

Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD) -Haplo-Identical Only See intervention descriptions.

Treatment:

Drug: Osteopetrosis Haploidentical Only Preparative Regimen

Biological: Stem Cell Transplantation

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

Experimental group

Description:

See intervention descriptions.

Treatment:

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

Drug: IMD Preparative Regimen

Biological: Stem Cell Transplantation

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

Experimental group

Description:

See intervention descriptions.

Treatment:

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

Drug: IMD Preparative Regimen

Biological: Stem Cell Transplantation

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

Experimental group

Description:

See intervention descriptions.

Treatment:

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

Drug: IMD Preparative Regimen

Biological: Stem Cell Transplantation

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

Experimental group

Description:

See intervention descriptions.

Treatment:

Drug: IMD Preparative Regimen

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

Biological: Stem Cell Transplantation