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Trial record 14 of 17 for:    Sandhoff Disease

Stem Cell Transplant for Inborn Errors of Metabolism

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ClinicalTrials.gov Identifier: NCT00176904
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : June 10, 2011
Last Update Posted : December 28, 2017
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

September 12, 2005
September 15, 2005
May 17, 2011
June 10, 2011
December 28, 2017
January 1995
June 2010   (Final data collection date for primary outcome measure)
Overall Survival [ Time Frame: 100 Days, 1 Year and 3 Years ]
Number of patients alive at designated timepoints after transplant.
We will evaluate whether patients treated by bone marrow, peripheral blood, or umbilical cord blood transplantation after March of 2001 have equivalent or better outcome than historical controls with BMT for these patients over the last 5 years.
Complete list of historical versions of study NCT00176904 on ClinicalTrials.gov Archive Site
  • Overall Donor Engraftment [ Time Frame: Day 100 ]
    Number of patients with full donor chimerism (state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease) by Day 100 post-transplant of at least 90%.
  • Number of Patients With Grade II-IV Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ]
    Number of patients who exhibited acute graft-versus-host disease by Day 100 post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Grade I=mild, Grade II=moderate, Grade III=severe, Grade IV=life threatening.
  • Number of Patients With Grade III-IV Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ]
    Number of patients who exhibited acute graft-versus-host disease by Day 100 post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Grade I=mild, Grade II=moderate, Grade III=severe, Grade IV=life threatening.
  • Number of Patients With Chronic Graft-Versus-Host Disease [ Time Frame: 1 Year Post Transplant ]
    Number of patients who exhibited chronic graft-versus-host disease by 1 Year post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Chronic GVHD is an extension of this syndrome.
  • estimate survival at 100 days, 1 year and 3 years.
  • estimate change in neuropsychometric function at 6 months, 1 year, 2 years and 3 years.
  • estimate the toxicity of hematopoietic cell transplant therapy:
  • estimate the rate of hematological donor cell engraftment.
  • estimate the incidence of graft-versus-host disease (GVHD).
Not Provided
Not Provided
 
Stem Cell Transplant for Inborn Errors of Metabolism
Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation
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.

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.

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adrenoleukodystrophy
  • Metachromatic Leukodystrophy
  • Globoid Cell Leukodystrophy
  • Gaucher's Disease
  • Fucosidosis
  • Wolman Disease
  • Niemann-Pick Disease
  • Batten Disease
  • GM1 Gangliosidosis
  • Tay Sachs Disease
  • Sandhoff Disease
  • Procedure: Stem Cell Transplant
    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).
    Other Name: Bone marrow transplant
  • Drug: Busulfan, Cyclophosphamide, Antithymocyte Globulin
    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.
    Other Name: Busulfex, Cytoxan, ATG
Experimental: Treated Patients
All patients treated with protocol regimen (chemotherapy and surgery).
Interventions:
  • Procedure: Stem Cell Transplant
  • Drug: Busulfan, Cyclophosphamide, Antithymocyte Globulin
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
135
75
June 2010
June 2010   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
Child, Adult, Older Adult
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00176904
MT1995-01
No
Not Provided
Not Provided
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP