Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism

NCT00668564 | Terminated Phase 2 Results DMC

• 2 other identifiers: MT2008-020801M25202
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this clinical trial is to evaluate the ability to achieve and sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of metabolism undergoing hematopoietic stem cell transplantation (HCT).

Conditions

Hurler's Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Sphingolipidoses; Krabbe Disease; Wolman's Disease; Niemann-Pick Disease Type B; Niemann-Pick Disease, Type C

Keywords

Inborn errors of metabolism; Sphingolipidoses; Recessive Leukodystrophies- GLD, Krabbe disease, MLD; Peroxisomal Disorders; Wolman syndrome; Niemann-Pick B patients; Niemann-Pick C subtype 2

Outcome Measures

Primary Outcomes (1)

• Number of Patients Achieving Engraftment

  Rate of successful engraftment - patients who achieved and sustained donor engraftment; donor chimerism by day 100 of at least 90% after undergoing hematopoietic stem cell transplantation.

  Day 100

Secondary Outcomes (1)

• Overall Survival

  Day 100, 1 Year, 3 Years

Study Arms (1)

Intent-to-Treat

EXPERIMENTAL

All patients treated with study regimen.

Procedure: Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Campath-1H; Drug: Busulfan

Interventions

Stem Cell Transplantation PROCEDURE

The purpose of hematopoietic stem cell transplantation is to introduce blood producing cells from a normal donor. These cells can either provide what is missing in the body to the other cells, or can change the body's immune response to the substances that have accumulated in the body. These normal hematopoietic stem cells can come from bone marrow, peripheral blood (i.e., the blood circulating in our body's blood vessels) or umbilical cord blood (i.e., blood taken from the umbilical cord after a baby is born and umbilical cord is cut). The new donor cells repopulate the blood and bone marrow system and enter the organs of the body, including the brain. Wherever these cells go, they will produce the needed enzyme.

Also known as: Bone Marrow Transplant, cord blood transplant

Intent-to-Treat

Cyclophosphamide DRUG

Days before Transplant Drug Frequency * 4 Cyclophosphamide Once, given over 2 hours * 3 Cyclophosphamide Once, given over 2 hours * 2 Cyclophosphamide Once, given over 2 hours * 1 Cyclophosphamide Once, given over 2 hours

Also known as: Cytoxan

Intent-to-Treat

Campath-1H DRUG

Days before Transplant Drug Frequency 12 Campath-1H Once, given over 2 hours 11 Campath-1H Once, given over 2 hours 10 Campath-1H Once, given over 2 hours

Also known as: Alemtuzamab

Intent-to-Treat

Busulfan DRUG

Days before Transplant Drug Frequency 9 Busulfan Four times per day 8 Busulfan Four times per day 7 Busulfan Four times per day 6 Busulfan Four times per day

Also known as: Busulfex

Intent-to-Treat

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Mucopolysaccharidosis (MPS) Disorders:
• MPS IH (Hurler syndrome)
• MPS-VI (Maroteaux-Lamy syndrome)
• MPS VII (Sly syndrome).
• Glycoprotein metabolic disorders:
• Alpha mannosidosis
• Fucosidosis
• Aspartylglucosaminuria
• Other Inherited Diseases of Metabolism:
• Wolman syndrome (acid lipase deficiency)
• Niemann-Pick B patients (sphingomyelin deficiency)
• Niemann-Pick C subtype 2
• Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program: Priority will be as follows, although in circumstances in which timing is of the essence, cord blood grafts may be chosen over an unrelated graft, despite the priority listed above.
• Multidisciplinary Evaluation: Patients will be eligible for transplantation only after they are seen and evaluated by members of the Inherited Metabolic and Storage Disease Program (IMSD) team, and the team has offered transplantation to the patient/family.

You may not qualify if:

• Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be considered for other treatment protocols.
• Major organ dysfunction. Evidence of major organ impairment, including:
• Cardiac: left ventricular ejection fraction \<40%
• Renal: serum creatinine \>2.5 x normal for age
• Hepatic: total bilirubin \>3 x normal, or Alanine transaminase (ALT) \> 3 x normal
• Pulmonary: requirement for continuous oxygen supplementation
• Pregnancy
• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
• Patients \>21 years of age.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota, Fairview

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• Miller WP, Rothman SM, Nascene D, Kivisto T, DeFor TE, Ziegler RS, Eisengart J, Leiser K, Raymond G, Lund TC, Tolar J, Orchard PJ. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011 Aug 18;118(7):1971-8. doi: 10.1182/blood-2011-01-329235. Epub 2011 May 17.

  PMID: 21586746 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Mucopolysaccharidosis VII; alpha-Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Sphingolipidoses; Leukodystrophy, Globoid Cell; Wolman Disease; Niemann-Pick Disease, Type B; Niemann-Pick Disease, Type C; Metabolism, Inborn Errors; Leukodystrophy, Metachromatic; Peroxisomal Disorders

Interventions

Stem Cell Transplantation; Bone Marrow Transplantation; Cyclophosphamide; Alemtuzumab; Busulfan

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate 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; Mannosidase Deficiency Diseases; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Cholesterol Ester Storage Disease; Infant, Newborn, Diseases; Niemann-Pick Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Sulfatidosis

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

Other secondary objectives outlined in study protocol were not analyzed; number of patients were too few to be relevant.

Results Point of Contact

• Title: Paul Orchard, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

orcha001@umn.edu

612-626-2313

Study Officials

• Paul Orchard, MD

  University of Minnesota Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 29, 2008
• Study Start: March 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: December 28, 2017
• Results First Posted: July 13, 2011

Record last verified: 2017-12

Locations

US (1)