Clinical trial
MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
Name
2013LS104
Description
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).
Trial arms
Trial start
2014-07-10
Estimated PCD
2025-07-14
Trial end
2028-07-14
Status
Recruiting
Phase
Early phase I
Treatment
Stem Cell Transplantation
Infusion given on Day 0
Arms:
IMD - Except Haplo-identical, OP - Except Haplo-Identical, OP and IMD -Haplo-Identical Only, cALD HR-C (High-Risk, Regimen C), cALD HR-D (High-Risk, Regimen D), cALD SR-A (Standard-Risk, Regimen A), cALD SR-B (Standard-Risk, Regimen B)
IMD Preparative Regimen
* Anti-thymocyte Globulin (ATG)
* Fludarabine
* Busulfan
Arms:
IMD - Except Haplo-identical, cALD HR-C (High-Risk, Regimen C), cALD HR-D (High-Risk, Regimen D), cALD SR-A (Standard-Risk, Regimen A), cALD SR-B (Standard-Risk, Regimen B)
Osteopetrosis Only Preparative Regimen
* Anti-thymocyte Globulin (ATG)
* Fludarabine
* Busulfan
* Thiotepa
Arms:
OP - Except Haplo-Identical
Osteopetrosis Haploidentical Only Preparative Regimen
* Rituximab
* Alemtuzumab
* Busulfan
* Fludarabine
Arms:
OP and IMD -Haplo-Identical Only
cALD SR-A (Standard-Risk, Regimen A)
N-acetylcysteine start day +1 through day +28
Arms:
cALD SR-A (Standard-Risk, Regimen A)
cALD SR-B (Standard-Risk, Regimen B)
N-acetylcysteine start day +1through day +56
Arms:
cALD SR-B (Standard-Risk, Regimen B)
cALD HR-D (High-Risk, Regimen C)
N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100
Arms:
cALD HR-C (High-Risk, Regimen C)
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
Arms:
cALD HR-D (High-Risk, Regimen D)
Size
100
Primary endpoint
Percent of subjects who achieve high-level donor hematopoietic engraftment
Day +42 post-transplant
Percent of subjects who achieve high-level donor hematopoietic engraftment
Day +100 post-transplant
Eligibility criteria
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)
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 100, 'type': 'ESTIMATED'}}
Updated at
2023-11-03
1 organization
7 products
29 indications
Organization
Masonic Cancer Center, University of MinnesotaProduct
Stem Cell TransplantationIndication
Mucopolysaccharidosis DisordersIndication
Hurler syndromeIndication
Mucopolysaccharidosis II (MPS II)Indication
Maroteaux Lamy SyndromeIndication
Sly SyndromeIndication
alpha-mannosidosisIndication
FucosidosisIndication
AspartylglucosaminuriaIndication
Glycoprotein Metabolic DisordersIndication
SphingolipidosesIndication
recessive leukodystrophiesIndication
Globoid Cell LeukodystrophyIndication
Metachromatic LeukodystrophyIndication
Niemann-Pick BIndication
Niemann-Pick C Subtype 2Indication
Niemann-Pick diseaseIndication
Peroxisomal DisordersIndication
AdrenoleukodystrophyIndication
Zellweger SyndromeIndication
Neonatal AdrenoleukodystrophyIndication
Infantile Refsum DiseaseIndication
Acyl-CoA Oxidase DeficiencyIndication
D-Bifunctional Enzyme DeficiencyIndication
Multifunctional Enzyme DeficiencyIndication
Alpha-methylacyl-CoA Racmase DeficiencyIndication
OsteopetrosisIndication
Inherited Metabolic DisordersProduct
IMD Preparative RegimenProduct
OsteopetrosisProduct
CALD SR-AProduct
cALD SR-BProduct
cALD HR-D