Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

NCT01043640 | Completed Phase 2 Results DMC

• 2 other identifiers: 2009LS088MT2009-19
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mucopolysaccharidosis; Hurler Syndrome; Hunter Syndrome; Maroteaux-Lamy Syndrome; Sly Syndrome; Alpha Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy (ALD); Krabbe Disease; Metachromatic Leukodystrophy (MLD); Sphingolipidoses; Peroxisomal Disorders

Keywords

inherited metabolic disorders

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Donor Derived Engraftment

  Donor derived engraftment is defined as 80 percent or greater donor cells in the recipient's bone marrow and blood cells.

  Day 100 Post Transplant

Secondary Outcomes (11)

• Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

• Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

• Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

• Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

• Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)

  Day 100 Post Transplant

Study Arms (1)

Transplant Patients

EXPERIMENTAL

Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan.

Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Busulfan; Procedure: Allogeneic stem cell transplantation; Drug: Cyclosporine A; Drug: Mycophenolate Mofetil

Interventions

Campath-1H DRUG

Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV)

Also known as: Alemtuzumab

Transplant Patients

Cyclophosphamide DRUG

Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.

Also known as: Cytoxan(R)

Transplant Patients

Busulfan DRUG

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

Also known as: Busulfex(R)

Transplant Patients

Allogeneic stem cell transplantation PROCEDURE

Administered \> 24 hours after last dose of busulfan.

Also known as: stem cell transplant

Transplant Patients

Cyclosporine A DRUG

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).

Also known as: CsA

Transplant Patients

Mycophenolate Mofetil DRUG

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.

Also known as: MMF

Transplant Patients

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI; Mucopolysaccharidosis VII; alpha-Mannosidosis; Fucosidosis; Aspartylglucosaminuria; Adrenoleukodystrophy; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Sphingolipidoses; Peroxisomal Disorders

Interventions

Alemtuzumab; Cyclophosphamide; Busulfan; Stem Cell Transplantation; Cyclosporine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Mannosidase Deficiency Diseases; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Sulfatidosis

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Paul Orchard
• Organization: Masonic Cancer Center, University of Minnesota

orcha001@umn.edu

612-626-2313

Study Officials

• Paul Orchard, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2010
• First Posted: January 7, 2010
• Study Start: December 1, 2009
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2017
• Last Updated: February 5, 2018
• Results First Posted: May 12, 2017

Record last verified: 2017-09

Locations

US (1)