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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

Tracking Information
First Submitted Date  ICMJE September 12, 2005
First Posted Date  ICMJE September 15, 2005
Results First Submitted Date May 17, 2011
Results First Posted Date June 10, 2011
Last Update Posted Date December 28, 2017
Study Start Date  ICMJE January 1995
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2011)
Overall Survival [ Time Frame: 100 Days, 1 Year and 3 Years ]
Number of patients alive at designated timepoints after transplant.
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2005)
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.
Change History Complete list of historical versions of study NCT00176904 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2011)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2005)
  • 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).
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Stem Cell Transplant for Inborn Errors of Metabolism
Official Title  ICMJE Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation
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.

Study Type  ICMJE Interventional
Study Phase Phase 2
Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adrenoleukodystrophy
  • Metachromatic Leukodystrophy
  • Globoid Cell Leukodystrophy
  • Gaucher's Disease
  • Fucosidosis
  • Wolman Disease
  • Niemann-Pick Disease
  • Batten Disease
  • GM1 Gangliosidosis
  • Tay Sachs Disease
  • Sandhoff Disease
Intervention  ICMJE
  • 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
Study Arms Experimental: Treated Patients
All patients treated with protocol regimen (chemotherapy and surgery).
Interventions:
  • Procedure: Stem Cell Transplant
  • Drug: Busulfan, Cyclophosphamide, Antithymocyte Globulin
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 17, 2011)
135
Original Enrollment  ICMJE
 (submitted: September 12, 2005)
75
Actual Study Completion Date June 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00176904
Other Study ID Numbers  ICMJE MT1995-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2017

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