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

Phase 2

Recruiting

• Conditions: Maroteaux Lamy Syndrome; Alpha-Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Glycoprotein Metabolic Disorders; Niemann-Pick B; Adrenoleukodystrophy With Cerebral Involvement; Zellweger Syndrome; D-Bifunctional Enzyme Deficiency; Inherited Metabolic Disorders
• Interventions: Biological: Stem Cell Transplantation; Drug: IMD Preparative Regimen; Drug: Osteopetrosis Only Preparative Regimen; Drug: Osteopetrosis Haploidentical Only Preparative Regimen; Drug: cALD HR-D (High-Risk, Regimen C); Drug: cALD SR-B (Standard-Risk, Regimen B); Drug: cALD SR-A (Standard-Risk, Regimen A); Drug: cALD HR-D (High-Risk, Regimen D)

• Registration Number: NCT02171104
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-06-20
• Study First Submitted QC: 2014-06-20
• Study First Posted: 2014-06-23
• Study Start: 2014-07-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-04
• Last Update Posted: 2024-11-05
• Primary Completion: 2025-07-14
• Study Completion: 2028-07-14

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cALD SR-A (Standard-Risk, Regimen A)	IMD Preparative Regimen	See intervention descriptions.
cALD HR-D (High-Risk, Regimen D)	IMD Preparative Regimen	See intervention descriptions.
cALD HR-D (High-Risk, Regimen D)	Stem Cell Transplantation	See intervention descriptions.
cALD HR-C (High-Risk, Regimen C)	Stem Cell Transplantation	See intervention descriptions.
cALD HR-C (High-Risk, Regimen C)	IMD Preparative Regimen	See intervention descriptions.
cALD HR-C (High-Risk, Regimen C)	cALD HR-D (High-Risk, Regimen C)	See intervention descriptions.
OP - Except Haplo-Identical	Stem Cell Transplantation	Severe Osteoperosis (OP) - Except Haplo-Identical See intervention descriptions.
OP - Except Haplo-Identical	Osteopetrosis Only Preparative Regimen	Severe Osteoperosis (OP) - Except Haplo-Identical See intervention descriptions.
IMD - Except Haplo-identical	Stem Cell Transplantation	Inherited Metabolic Disease (IMD) - Except Haplo-Identical See intervention descriptions.
IMD - Except Haplo-identical	IMD Preparative Regimen	Inherited Metabolic Disease (IMD) - Except Haplo-Identical See intervention descriptions.
OP and IMD -Haplo-Identical Only	Stem Cell Transplantation	Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD) -Haplo-Identical Only See intervention descriptions.
cALD SR-B (Standard-Risk, Regimen B)	IMD Preparative Regimen	See intervention descriptions.
cALD SR-B (Standard-Risk, Regimen B)	cALD SR-B (Standard-Risk, Regimen B)	See intervention descriptions.
cALD SR-B (Standard-Risk, Regimen B)	Stem Cell Transplantation	See intervention descriptions.
OP and IMD -Haplo-Identical Only	Osteopetrosis Haploidentical Only Preparative Regimen	Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD) -Haplo-Identical Only See intervention descriptions.
cALD SR-A (Standard-Risk, Regimen A)	Stem Cell Transplantation	See intervention descriptions.
cALD SR-A (Standard-Risk, Regimen A)	cALD SR-A (Standard-Risk, Regimen A)	See intervention descriptions.
cALD HR-D (High-Risk, Regimen D)	cALD HR-D (High-Risk, Regimen D)	See intervention descriptions.

Primary Outcome Measures

Name	Time	Method
Percent of subjects who achieve high-level donor hematopoietic engraftment	Day +100 post-transplant	Defined as ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant

Secondary Outcome Measures

Name	Time	Method
Graft-versus-host disease	Day +100 post-transplant	Incidence and severity of GvHD
Regimen-related toxicity	Day +100 post-transplant	Defined as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease
Post-HSCT changes in disease	2 years	Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Transplant-related mortality	Day +100 post-transplant	Incidence of TRM

Trial Locations

Locations (1)

Masonic Cancer Center, University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States