Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

NCT01372228 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ICT-14070-010611
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to establish chimerism and avoid graft-versus-host-disease (GVHD) in patients with inherited metabolic disorders.

Conditions

Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis

Keywords

hematopoietic stem cell Tx, chimerism, leukodystrophy

Outcome Measures

Primary Outcomes (1)

• Production of missing enzyme at levels greater than or equal to 10% of normal

  Day 180 post transplant to three years

Secondary Outcomes (1)

• Enriched Hematopoetic Stem Cell Engraftment

  One month to three years

Study Arms (1)

Inherited Metabolic Disorder Patients

EXPERIMENTAL

Recipients are treated with hematopoietic stem cell infusion from living donors

Biological: hematopoietic stem cell infusion

Interventions

hematopoietic stem cell infusion BIOLOGICAL

Enriched hematopoetic stem cell infusion

Inherited Metabolic Disorder Patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a confirmed diagnosis of inherited metabolic disorder / inborn error of metabolism. Diagnosis should be confirmed by appropriate test(s) (enzyme and/or mutation analysis) before study entry. Patients must not be eligible for myeloablative chemotherapy as a preparative regimen for transplant due to age, co-morbidities or organ dysfunction.
• Inborn errors of metabolism / Inherited Metabolic Disorders (IMD) eligible for this study include the following:
• Hurler Syndrome (MPS I)
• Hurler-Scheie Syndrome with early neurologic involvement and/or sensitization to ERT
• Hunter Syndrome (MPS II)
• Sanfilippo Syndrome (MPS III)
• Krabbe Disease (Globoid Leukodystrophy)
• Metachromatic Leukodystrophy (MLD)
• Adrenoleukodystrophy (ALD and AMN)
• Sandhoff Disease
• Tay Sachs Disease
• Pelizaeus Merzbacher (PMD)
• Niemann-Pick Disease
• Alpha-mannosidosis
• Patients must have adequate function of other organ systems as measured by:

You may not qualify if:

• Patients with uncontrolled seizures, apnea, evidence of recurrent or uncontrolled aspiration, or need for chronic mechanical ventilation.
• Patients with allogeneic stem cell transplant with cytoreductive therapy in the past 6 months.
• Subjects must not have had previous radiation therapy that would preclude total body irradiation (TBI) (as determined by radiation therapist)
• Uncontrolled infection or severe concomitant diseases, which in the judgment of the Principal Investigator, could not tolerate reduced intensity transplantation.
• Subjects with a positive human immunodeficiency virus (HIV) antibody test result
• Subjects who are pregnant, as indicated by a positive serum human chorionic gonadotropin (HCG) test
• Subjects whose only donor is pregnant at the time of intended transplant
• Subjects of childbearing potential who are not practicing adequate contraception as defined by the investigator at the site
• Jehovah's witnesses being unwilling to be transfused
• Patients that have any comorbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.
• Lack of related donors

Sponsors & Collaborators

• Talaris Therapeutics Inc.: lead
• Duke University: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I; Mucopolysaccharidosis II; Sudden Infant Death; Mucopolysaccharidosis III; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Adrenoleukodystrophy; Sandhoff Disease; Tay-Sachs Disease; Niemann-Pick Diseases; alpha-Mannosidosis

Interventions

Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death; Hereditary Central Nervous System Demyelinating Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Leukoencephalopathies; Demyelinating Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Sulfatidosis; Peroxisomal Disorders; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Gangliosidoses, GM2; Gangliosidoses; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Mannosidase Deficiency Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Suzanne T Ildstad, MD

  Talaris Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 10, 2011
• First Posted: June 13, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

US (1)