Stem Cell Transplant for Inborn Errors of Metabolism

NCT00176904 | Completed Phase 2 Results

• 1 other identifier: MT1995-01
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for an inherited metabolic storage disease.

Conditions

Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

Keywords

Inborn errors; Storage disease; errors of metabolism; stem cell transplant

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Number of patients alive at designated timepoints after transplant.

  100 Days, 1 Year and 3 Years

Secondary Outcomes (4)

• Overall Donor Engraftment

  Day 100

• Number of Patients With Grade II-IV Acute Graft-Versus-Host Disease

  Day 100

• Number of Patients With Grade III-IV Acute Graft-Versus-Host Disease

  Day 100

• Number of Patients With Chronic Graft-Versus-Host Disease

  1 Year Post Transplant

Study Arms (1)

Treated Patients

EXPERIMENTAL

All patients treated with protocol regimen (chemotherapy and surgery).

Procedure: Stem Cell Transplant; Drug: Busulfan, Cyclophosphamide, Antithymocyte Globulin

Interventions

Stem Cell Transplant PROCEDURE

The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains an enzyme able to get rid of the substances that have accumulated in the body of patients with storage diseases. Hematopoietic 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).

Also known as: Bone marrow transplant

Treated Patients

Busulfan, Cyclophosphamide, Antithymocyte Globulin DRUG

Subjects will receive BUSULFAN intravenously (IV)- patients \< or= 12 kg 1.1 mg/kd/dose IV every 6 hours for 16 doses; patients \> 12kg 0.8 mg/kg/dose IV every 6 hours for 16 doses - via the Hickman line four times daily for 4 days, CYCLOPHOSPHAMIDE intravenously (50 mg/kg/day IV over 2 hours) via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV (15 mg/kg/day over 2 hours) via the Hickman line twice daily for three days before the transplant. These three drugs are being given to help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.

Also known as: Busulfex, Cytoxan, ATG

Treated Patients

Eligibility Criteria

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

You may qualify if:

• Patients with adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy, Gaucher's disease, Fucosidosis, Wolman disease, Niemann-Pick disease and Batten disease (CLN3) who have a human leukocyte antigen (HLA)-identical or haplotype mismatched (at 1-3 antigens) related marrow, or umbilical cord blood donor. One or two umbilical cord blood (UCB) units may be used.
• Patients with GM1 gangliosidosis, Tay Sachs disease or Sandhoff disease who have a HLA-identical or 1 antigen mismatched related or unrelated donor, or suitably matched umbilical cord blood unit(s). One or two UCB units may be used.
• Patients with adrenoleukodystrophy must have magnetic resonance imaging (MRI) findings, neurological and neuropsychometric function consistent with the diagnosis, and for boys with parietal-occipital dysmyelination a performance intelligence quotient (IQ) ≥80. In cases, when the performance IQ is not ≥80, the protocol committee may recommend transplant if the patient's clinical condition and neuropsychometric status are deemed to be acceptable based upon consideration of such factors as age at onset of cerebral disease, magnitude of change in performance IQ and neurologic deficits.
• Patients with arylsulfatase A deficiency (Metachromatic Leukodystrophy) must have either the presymptomatic late infantile, juvenile or adult form of the disease and must have acceptable neurological and neuropsychometric function.
• Patients with galactocerebrosidase deficiency (Globoid Cell Leukodystrophy) must have acceptable neurological and neuropsychometric function.
• Patients with acid lipase deficiency (Wolman disease) must have a liver biopsy that documents no evidence of hepatic cirrhosis, and acceptable neurological and neuropsychometric function.
• Patients with fucosidase deficiency (Fucosidosis) must have acceptable neurological and neuropsychometric function.
• Patients with glucocerebrosidase deficiency (Gaucher's Disease) must have acceptable neurologic and neuropsychometric function.
• Patients with Batten's disease (CLN3) must have acceptable Neurological and neuropsychometric function.
• Absence of major organ dysfunction. Organ evaluation results as follows:
• Cardiac: ejection fraction \>30%
• Renal: serum creatinine \<2x normal or creatinine clearance 60 mL/min.
• Hepatic: total bilirubin \<2x normal and Aspartate aminotransferase (AST) \<2x normal
• Signed consent.

You may not qualify if:

• Patients with symptomatic late infantile form of metachromatic leukodystrophy.
• Patients with symptomatic infantile globoid leukodystrophy.
• Note: Patients with Hurler syndrome, mucopolysaccharidosis (MPS) VI, or Mannosidosis disease are no longer eligible for this protocol, but can be transplanted under protocol MT 9907 (NCT00176917 - Hematopoietic Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)).
• Pregnancy
• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
• Patients or parents are psychologically incapable of undergoing bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance.
• Patients ≥ 50 kg may be at risk for having cell doses below the goal of ≥ 10 x 10\^6 CD34 cells/kg and therefore will not be eligible to receive unrelated peripheral blood stem cells (PBSCs)

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

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

Adrenoleukodystrophy; Leukodystrophy, Metachromatic; Leukodystrophy, Globoid Cell; Gaucher Disease; Fucosidosis; Wolman Disease; Niemann-Pick Diseases; Neuronal Ceroid-Lipofuscinoses; Gangliosidosis, GM1; Tay-Sachs Disease; Sandhoff Disease

Interventions

Stem Cell Transplantation; Bone Marrow Transplantation; Busulfan; Cyclophosphamide; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Sulfatidosis; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Carbohydrate Metabolism, Inborn Errors; Cholesterol Ester Storage Disease; Infant, Newborn, Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Neurodegenerative Diseases; Gangliosidoses; Gangliosidoses, GM2

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Change in Neuropsychometric function data is not available. Data would have been noted as descriptive and patient specific, as well as disease specific; not table format. No formal analysis was intended.

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

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: January 1, 1995
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 28, 2017
• Results First Posted: June 10, 2011

Record last verified: 2017-12

Locations

US (1)