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CompletedNCT01043640Updated Feb 5, 2018Results posted

Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders

A Phase 2 interventional study of Campath-1H and Cyclophosphamide in Mucopolysaccharidosis, Hurler Syndrome and Hunter Syndrome, sponsored by Masonic Cancer Center, University of Minnesota. Completed at 1 site in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2018-02-05.

Sponsored by Masonic Cancer Center, University of Minnesota · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
46
Allocation
Not applicable
Ages
Up to 21 Years
Sex
All
01

Study 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.

Read the 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.
02

Conditions studied

  • 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
03

In context

Mucopolysaccharidoses

59 studies on the registry are indexed under Mucopolysaccharidoses; 11 are open to participants now.

This study's enrollment of 46 is above the median of 12 across 27 interventional studies indexed under Mucopolysaccharidoses.

Browse Mucopolysaccharidoses studies →

Lead sponsor

Masonic Cancer Center, University of Minnesota is the lead sponsor of 286 studies on the registry; 35 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Browse Masonic Cancer Center, University of Minnesota studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion Criteria:

  • Pregnant - menstruating females must have a negative serum pregnancy test within 14 days of treatment start
  • Evidence of (HIV) infection or known HIV positive serology
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
46 participants (actual)

Study arms

  • 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 · Drug: Cyclophosphamide · Drug: Busulfan · Procedure: Allogeneic stem cell transplantation · Drug: Cyclosporine A · Drug: Mycophenolate Mofetil

Interventions

  • DrugCampath-1H

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

    Also known as: Alemtuzumab

  • DrugCyclophosphamide

    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)

  • DrugBusulfan

    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)

  • ProcedureAllogeneic stem cell transplantation

    Administered \> 24 hours after last dose of busulfan.

    Also known as: stem cell transplant

  • DrugCyclosporine 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).

    Also known as: CsA

  • DrugMycophenolate 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.

    Also known as: MMF

06

What researchers measure

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.

    Time frame: Day 100 Post Transplant

Secondary outcomes

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

    GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

    Time frame: Day 100 Post Transplant

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

    GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

    Time frame: Day 100 Post Transplant

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

    GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

    Time frame: Day 100 Post Transplant

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

    GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

    Time frame: Day 100 Post Transplant

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

    GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

    Time frame: Day 100 Post Transplant

  6. Number of Patients Who Died Peri-Transplant

    Peri-transplant is defined as within 100 days of transplant.

    Time frame: By Day 100 Post Transplant

  7. Donor Cell Chimerism Following Transplant

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

    Time frame: Day 28

  8. Donor Cell Chimerism Following Transplant

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

    Time frame: Day 42

  9. Donor Cell Chimerism Following Transplant

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

    Time frame: Day 100

  10. Donor Cell Chimerism Following Transplant

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

    Time frame: 6 months

  11. Donor Cell Chimerism Following Transplant

    Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

    Time frame: One year

07

Results

Posted May 12, 2017

Participant flow

Participant flow — Overall Study
MilestoneTransplant Patients
Started46
Completed46
Not completed0

Outcome measures

PrimaryNumber 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.

Time frame:
Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients With Donor Derived Engraftment
ParticipantsTransplant Patients
Number of Patients With Donor Derived Engraftment42
SecondaryNumber of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)

GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

Time frame:
Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)
ParticipantsTransplant Patients
Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)32
SecondaryNumber of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)

GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

Time frame:
Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)
ParticipantsTransplant Patients
Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)2
SecondaryNumber of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)

GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

Time frame:
Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)
ParticipantsTransplant Patients
Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)5
SecondaryNumber of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)

GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

Time frame:
Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)
ParticipantsTransplant Patients
Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)2
SecondaryNumber of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)

GVHD grading is performed using modified Glucksberg criteria and is as follows: grade 0: absence of any skin, liver and/or gastrointestinal (GI) involvement grade 1: skin stage 1 or 2 only grade 2: skin stage 3 or liver stage 1 or lower GI stage 1 or upper GI involvement grade 3: skin stage 0 - 3 plus liver stage 2-4 or lower GI stage 2-3 grade 4: skin stage 4 or lower GI stage 4

Time frame:
Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)
ParticipantsTransplant Patients
Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)5
SecondaryNumber of Patients Who Died Peri-Transplant

Peri-transplant is defined as within 100 days of transplant.

Time frame:
By Day 100 Post Transplant
Reported as:
Count of participants · Participants
Number of Patients Who Died Peri-Transplant
ParticipantsTransplant Patients
Number of Patients Who Died Peri-Transplant2
SecondaryDonor Cell Chimerism Following Transplant

Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

Time frame:
Day 28
Reported as:
Mean · percentage of donor cells
Donor Cell Chimerism Following Transplant
percentage of donor cellsTransplant Patients
Donor Cell Chimerism Following Transplant95 ± 9
SecondaryDonor Cell Chimerism Following Transplant

Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

Time frame:
Day 42
Reported as:
Mean · percentage of donor cells
Donor Cell Chimerism Following Transplant
percentage of donor cellsTransplant Patients
Donor Cell Chimerism Following Transplant93 ± 15
SecondaryDonor Cell Chimerism Following Transplant

Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

Time frame:
Day 100
Reported as:
Mean · percentage of donor cells
Donor Cell Chimerism Following Transplant
percentage of donor cellsTransplant Patients
Donor Cell Chimerism Following Transplant90 ± 26
SecondaryDonor Cell Chimerism Following Transplant

Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

Time frame:
6 months
Reported as:
Mean · percentage of donor cells
Donor Cell Chimerism Following Transplant
percentage of donor cellsTransplant Patients
Donor Cell Chimerism Following Transplant94 ± 22
SecondaryDonor Cell Chimerism Following Transplant

Donor cell chimerism is defined as the percentage of bone marrow and blood cells in the recipient that are of donor origin.

Time frame:
One year
Reported as:
Mean · percentage of donor cells
Donor Cell Chimerism Following Transplant
percentage of donor cellsTransplant Patients
Donor Cell Chimerism Following Transplant99 ± 4

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Transplant Patients—8/46 (17.4%)40/46 (87%)
Most frequent serious events
Most frequent serious events
EventTransplant Patients
Pericardial EffusionCardiac disorders2/46
DiarrheaGastrointestinal disorders2/46
Renal FailureRenal and urinary disorders1/46
Respiratory FailureRespiratory, thoracic and mediastinal disorders1/46
Pulmonary Veno-Occlusive DiseaseRespiratory, thoracic and mediastinal disorders1/46
Cardiac ArrestCardiac disorders1/46
Intracerebral HemorrhageNervous system disorders1/46
Most frequent other events
Showing 10 of 22
Most frequent other events
EventTransplant Patients
Infection, NOSInfections and infestations35/46
HypertensionVascular disorders21/46
Bilirubin IncreasedInvestigations16/46
DyspneaRespiratory, thoracic and mediastinal disorders14/46
HypoxiaRespiratory, thoracic and mediastinal disorders14/46
FeverGeneral disorders11/46
MucositisGastrointestinal disorders11/46
Hemorrhage, GenitourinaryRenal and urinary disorders10/46
RashSkin and subcutaneous tissue disorders10/46
Graft Versus Host DiseaseGeneral disorders9/46

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Transplant Patients
<=18 years46
Between 18 and 65 years0
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Transplant Patients
Female11
Male35
08

Study locations

1 site
  • Masonic Cancer Center, University of Minnesota
    Minneapolis, Minnesota 55455, United States
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Dec 2009, a primary completion of Jun 2015 and a completion of Jun 2017. It does not say whether these dates are actual or estimated.

Results were first posted in May 2017, 1 year 11 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 5, 2010
First posted
Jan 7, 2010
Start
Dec 2009
Primary completionActual
Jun 2015
CompletionActual
Jun 2017
Results first posted
May 12, 2017
Last update
Feb 5, 2018
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 5, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01043640
Lead sponsor
Masonic Cancer Center, University of Minnesota
Responsible party
Sponsor
First posted
Jan 7, 2010
Start date
Dec 2009
Primary completion
Jun 2015
Completion
Jun 2017
Results posted
May 12, 2017
Last update
Feb 5, 2018

Study contacts

Paul Orchard, MD
principal investigator · Masonic Cancer Center, University of Minnesota

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Alemtuzumab · Cyclophosphamide · Busulfan · Cyclosporine · Mycophenolic Acid

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