Clinical trial NCT00176904: Stem Cell Transplant for Inborn Errors of Metabolism
Official title: Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
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
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 135
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Prior to transplantation, subjects will receive Busulfan intravenously (IV) via the Hickman line four times daily for 4 days, Cyclophosphamide intravenously via the Hickman line once a day for 4 days, and Anti-Thymocyte Globulin (ATG) intravenously (IV) via the Hickman line twice daily for three days before the transplant. These three drugs are being given to subjects to help the new marrow "take" and grow.

On the day of transplantation, the donor's hematopoietic cells will be transfused via central venous catheter.

After hematopoietic cell transplant, subjects will then receive two drugs, cyclosporin and either methylprednisolone or Mycophenolate Mofetil (MMF). Cyclosporin and methylprednisolone or MMF are given to help prevent the complication of graft-versus-host disease and to decrease the chance that the new donor cells will be rejected.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Overall Survival
timeFrame: 100 Days, 1 Year and 3 Years
Secondary outcomes:
measure: Overall Donor Engraftment
timeFrame: Day 100
measure: Number of Patients With Grade II-IV Acute Graft-Versus-Host Disease
timeFrame: Day 100
measure: Number of Patients With Grade III-IV Acute Graft-Versus-Host Disease
timeFrame: Day 100
measure: Number of Patients With Chronic Graft-Versus-Host Disease
timeFrame: 1 Year Post Transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Paul Orchard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.