Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01043640
First received: January 5, 2010
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

Rationale: Chemotherapy administration before a donor stem cell transplant is necessary to stop the patient's immune system from rejecting the donor's stem cells. When healthy stem cells from a donor are infused into the patient, the donor white blood cells can provide the missing enzyme that causes the metabolic disease. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before transplant and cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. This may be an effective treatment for inherited metabolic disorders.

Purpose: The design of this study is to achieve donor cell engraftment in patients with standard-risk inherited metabolic diseases with limited peri-transplant morbidity and mortality. This will be achieved through the administration of the chemotherapy regimen described. The intention is to follow transplanted patient for years after transplant monitoring them for complications of their disease and assisting families with a multifaceted interdisciplinary approach.


Condition Intervention Phase
Mucopolysaccharidosis
Hurler Syndrome
Hunter Syndrome
Maroteaux-Lamy Syndrome
Sly Syndrome
Alpha Mannosidosis
Fucosidosis
Aspartylglucosaminuria
Adrenoleukodystrophy (ALD)
Krabbe Disease
Metachromatic Leukodystrophy (MLD)
Sphingolipidoses
Peroxisomal Disorders
Drug: Campath-1H
Drug: Cyclophosphamide
Drug: Busulfan
Procedure: Allogeneic stem cell transplantation
Drug: Cyclosporine A
Drug: Mycophenolate Mofetil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Number of Patients with Donor Derived Engraftment [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Patients with Graft-Versus-Host Disease (GVHD) by Severity [ Time Frame: Day 100 Post Transplant ] [ Designated as safety issue: No ]
  • Number of Patients Died Peri-Transplant [ Time Frame: By Day 100 Post Transplant ] [ Designated as safety issue: Yes ]
  • Donor Cell Chimerism Following Transplant [ Time Frame: Day 28, Day 42, Day 100, Month 6, Yearly Post Transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: December 2009
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Transplant Patients
Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.
Drug: Campath-1H
Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV)
Other Name: Alemtuzumab
Drug: Cyclophosphamide
Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.
Other Name: Cytoxan(R)
Drug: Busulfan
Administered every 6 hours: If < or = 12 kg then 1.1 mg/kg/dose intravenous (IV). If > 12 kg then 0.8 mg/kg/dose IV
Other Name: Busulfex(R)
Procedure: Allogeneic stem cell transplantation
Administered > 24 hours after last dose of busulfan.
Other Name: stem cell transplant
Drug: Cyclosporine A

2.5 mg/kg/dose intravenous (IV_ beginning on day -3. Frequency of daily dosing will be based on the recipient's body weight:

  • If body weight is ≤ 40 kg dosing will be 3 times daily
  • If body weight is > 40 kg dosing will be 2 times daily An attempt will be made to maintain a trough cyclosporine level of 250 mg/L to 350 mg/L. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CsA will be converted to an oral form at a dose 2 times the current IV dose (maximum 12.5 mg/kg/day as initial oral dose).
Other Name: CsA
Drug: Mycophenolate Mofetil
15 mg/kg/dose (max dose of 1gram) IV three times a day beginning on Day -3 at a dose based on body weight: The same dosage is used orally or intravenously. Stop MMF at day +42 or 7 days after engraftment achieved (ANC>500 x 10^6 neutrophils/L x 3 days and chimerism >90%), whichever is later.
Other Name: MMF

Detailed Description:

Primary Objective:

  • To estimate the proportion of patients with donor derived engraftment at day 100 post transplant as defined by 80% or greater donor cells in the CD3 (T cell) fraction

Secondary Objectives:

  • To determine the incidence and severity of graft-versus-host disease (GVHD) by day 100
  • To determine the incidence of peri-transplant mortality (death by day 100)
  • To monitor donor cell chimerism at various time points following allogeneic transplantation with this transplant regimen as determined at day 28, 42, 100, 6 months and yearly for 5 years.
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have diagnosis of one of the following: mucopolysaccharidosis disorder, glycoprotein metabolic disorder, sphingolipidoses or inherited leukodystrophy, peroxisomal disorder or other inherited diseases of metabolism
  • Must have an acceptable graft source as defined by University of Minnesota criteria
  • Adequate organ function

Exclusion Criteria:

  • Pregnant - menstruating females must have a negative serum pregnancy test within 14 days of treatment start
  • Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01043640

Contacts
Contact: Paul Orchard, MD 612-626-2961 orcha001@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Paul Orchard, MD    612-626-2961    orcha001@umn.edu   
Contact: Cyndie Hibbs    612-625-8542      
Principal Investigator: Paul Orchard, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01043640     History of Changes
Other Study ID Numbers: 2009LS088, MT2009-19
Study First Received: January 5, 2010
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
inherited metabolic disorders

Additional relevant MeSH terms:
Leukodystrophy, Globoid Cell
Leukodystrophy, Metachromatic
Fucosidosis
Alpha-Mannosidosis
Mannosidase Deficiency Diseases
Metabolic Diseases
Mucopolysaccharidoses
Mucopolysaccharidosis II
Mucopolysaccharidosis VI
Sphingolipidoses
Lipid Metabolism Disorders
Mucopolysaccharidosis VII
Mucopolysaccharidosis I
Adrenoleukodystrophy
Aspartylglucosaminuria
Peroxisomal Disorders
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Hereditary Central Nervous System Demyelinating Diseases
Leukoencephalopathies
Demyelinating Diseases
Lipidoses

ClinicalTrials.gov processed this record on July 28, 2014