Back to resultsMT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Primary Purpose
Mucopolysaccharidosis Disorders, Hurler Syndrome, Hunter Syndrome
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Stem Cell Transplantation
IMD Preparative Regimen
Osteopetrosis Only Preparative Regimen
Osteopetrosis Haploidentical Only Preparative Regimen
cALD SR-A (Standard-Risk, Regimen A)
cALD SR-B (Standard-Risk, Regimen B)
cALD HR-D (High-Risk, Regimen C)
cALD HR-D (High-Risk, Regimen D)
Sponsored by
About this trial
This is an interventional treatment trial for Mucopolysaccharidosis Disorders focused on measuring allogeneic hematopoietic cell transplantation, bone marrow transplantation, IMD, AMACRD, MNGIE, HDLS, OP, ALD
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)
Sites / Locations
- Masonic Cancer Center, University of MinnesotaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
IMD - Except Haplo-identical
OP - Except Haplo-Identical
OP and IMD -Haplo-Identical Only
cALD SR-A (Standard-Risk, Regimen A)
cALD SR-B (Standard-Risk, Regimen B)
cALD HR-C (High-Risk, Regimen C)
cALD HR-D (High-Risk, Regimen D)
Arm Description
Inherited Metabolic Disease (IMD) - Except Haplo-Identical See intervention descriptions.
Severe Osteoperosis (OP) - Except Haplo-Identical See intervention descriptions.
Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD) -Haplo-Identical Only See intervention descriptions.
See intervention descriptions.
See intervention descriptions.
See intervention descriptions.
See intervention descriptions.
Outcomes
Primary Outcome Measures
Percent of subjects who achieve high-level donor hematopoietic engraftment
Defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant
Percent of subjects who achieve high-level donor hematopoietic engraftment
Defined as ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant
Secondary Outcome Measures
Graft-versus-host disease
Incidence and severity of GvHD
Transplant-related mortality
Incidence of TRM
Regimen-related toxicity
Defined as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease
Post-HSCT changes in disease
Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Post-HSCT changes in disease
Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Full Information
NCT ID
NCT02171104
First Posted
June 20, 2014
Last Updated
November 1, 2022
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02171104
Brief Title
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Official Title
MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2014 (Actual)
Primary Completion Date
July 14, 2025 (Anticipated)
Study Completion Date
July 14, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
allogeneic hematopoietic cell transplantation, bone marrow transplantation, IMD, AMACRD, MNGIE, HDLS, OP, ALD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IMD - Except Haplo-identical
Arm Type
Experimental
Arm Description
Inherited Metabolic Disease (IMD) - Except Haplo-Identical
See intervention descriptions.
Arm Title
OP - Except Haplo-Identical
Arm Type
Experimental
Arm Description
Severe Osteoperosis (OP) - Except Haplo-Identical
See intervention descriptions.
Arm Title
OP and IMD -Haplo-Identical Only
Arm Type
Experimental
Arm Description
Severe Osteopetrosis (OP) and Inhterited Metabolic Disorders (IMD)
-Haplo-Identical Only
See intervention descriptions.
Arm Title
cALD SR-A (Standard-Risk, Regimen A)
Arm Type
Experimental
Arm Description
See intervention descriptions.
Arm Title
cALD SR-B (Standard-Risk, Regimen B)
Arm Type
Experimental
Arm Description
See intervention descriptions.
Arm Title
cALD HR-C (High-Risk, Regimen C)
Arm Type
Experimental
Arm Description
See intervention descriptions.
Arm Title
cALD HR-D (High-Risk, Regimen D)
Arm Type
Experimental
Arm Description
See intervention descriptions.
Intervention Type
Biological
Intervention Name(s)
Stem Cell Transplantation
Intervention Description
Infusion given on Day 0
Intervention Type
Drug
Intervention Name(s)
IMD Preparative Regimen
Intervention Description
Anti-thymocyte Globulin (ATG)
Fludarabine
Busulfan
Intervention Type
Drug
Intervention Name(s)
Osteopetrosis Only Preparative Regimen
Intervention Description
Anti-thymocyte Globulin (ATG)
Fludarabine
Busulfan
Thiotepa
Intervention Type
Drug
Intervention Name(s)
Osteopetrosis Haploidentical Only Preparative Regimen
Intervention Description
Rituximab
Alemtuzumab
Busulfan
Fludarabine
Intervention Type
Drug
Intervention Name(s)
cALD SR-A (Standard-Risk, Regimen A)
Intervention Description
N-acetylcysteine start day +1 through day +28
Intervention Type
Drug
Intervention Name(s)
cALD SR-B (Standard-Risk, Regimen B)
Intervention Description
N-acetylcysteine start day +1through day +56
Intervention Type
Drug
Intervention Name(s)
cALD HR-D (High-Risk, Regimen C)
Intervention Description
N-acetylcysteine and celecoxib start day of admission (prior to conditioning regimen) and continue through day +100
Intervention Type
Drug
Intervention Name(s)
cALD HR-D (High-Risk, Regimen D)
Intervention Description
N-acetylcysteine, celecoxib, vitamin E and alpha lipoic acid start day of admission (prior to conditioning regimen) and continue through day +100
Primary Outcome Measure Information:
Title
Percent of subjects who achieve high-level donor hematopoietic engraftment
Description
Defined as neutrophil recovery by Day +42 post-transplant and ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant
Time Frame
Day +42 post-transplant
Title
Percent of subjects who achieve high-level donor hematopoietic engraftment
Description
Defined as ≥ 80% donor cells on the myeloid fraction of peripheral blood at Day +100 post-transplant
Time Frame
Day +100 post-transplant
Secondary Outcome Measure Information:
Title
Graft-versus-host disease
Description
Incidence and severity of GvHD
Time Frame
Day +100 post-transplant
Title
Transplant-related mortality
Description
Incidence of TRM
Time Frame
Day +100 post-transplant
Title
Regimen-related toxicity
Description
Defined as infection, acute renal failure, respiratory failure, cardiac failure, and veno-occlusive disease
Time Frame
Day +100 post-transplant
Title
Post-HSCT changes in disease
Description
Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Time Frame
1 year
Title
Post-HSCT changes in disease
Description
Incidence of radiographic, physiologic, neuro-psychologic, and/or biochemical aspects of the disease as assessed on a disease-specific basis
Time Frame
2 years
10. Eligibility
Sex
All
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa Burke
Phone
612-273-8482
Email
lburke3@Fairview.org
First Name & Middle Initial & Last Name or Official Title & Degree
Troy Lund, M.D.Ph.D.
Phone
612-625-4185
Email
lundx072@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Orchard, M.D.
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Burke
Phone
612-273-8482
Email
lburke3@Fairview.org
12. IPD Sharing Statement
Learn more about this trial
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
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