Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders - Full Text View

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) Globoid Cell Leukodystrophy (GLD) 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:

Genetics Home Reference related topics: alpha-mannosidosis aspartylglucosaminuria Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis fucosidosis Krabbe disease leukoencephalopathy with vanishing white matter MECP2 duplication syndrome megalencephalic leukoencephalopathy with subcortical cysts metachromatic leukodystrophy mucopolysaccharidosis type I mucopolysaccharidosis type II mucopolysaccharidosis type VI mucopolysaccharidosis type VII PPM-X syndrome Renpenning syndrome Schindler disease succinic semialdehyde dehydrogenase deficiency X-linked adrenoleukodystrophy Zellweger spectrum

MedlinePlus related topics: Leukodystrophies Metabolic Disorders

Drug Information available for: Cyclophosphamide Busulfan Mycophenolic acid Mycophenolate sodium Cyclosporine Mycophenolate mofetil hydrochloride Mycophenolate mofetil Alemtuzumab

U.S. FDA Resources

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

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:	21 Years and older
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

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:	November 27, 2012
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
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
Lipid Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on May 19, 2013