Hurler's SyndromePhase 2NCT00668564
Hematopoietic Stem Cell Transplantation (HCT) for Inborn Errors of Metabolism
A Phase 2 study testing Stem Cell Transplantation, Cyclophosphamide and Campath-1H in people with Hurler's Syndrome and Maroteaux-Lamy Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
The primary objective of this clinical trial is to evaluate the ability to achieve and sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of metabolism undergoing hematopoietic stem cell transplantation (HCT). Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Hurler's Syndrome, Maroteaux-Lamy Syndrome, Sly Syndrome
- What is being tested?
- Stem Cell Transplantation, Cyclophosphamide and Campath-1H
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Feb 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Mucopolysaccharidosis (MPS) Disorders:
- MPS IH (Hurler syndrome)
- MPS-VI (Maroteaux-Lamy syndrome)
- MPS VII (Sly syndrome).
- Glycoprotein metabolic disorders:
- Alpha mannosidosis
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- Fucosidosis
- Aspartylglucosaminuria
- Sphingolipidoses and Recessive Leukodystrophies: Presymptomatic patients with globoid cell leukodystrophy (GLD, also known as Krabbe disease) and metachromatic leukodystrophy (MLD) will be eligible for treatment on this protocol. White matter disease by magnetic resonance imaging (MRI) alone is not an exclusion if the patient is asymptomatic.
- Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders associated with of very long chain fatty acids (VLCFA) elevation, identified by family history or laboratory testing (including neonatal screening), are eligible for this protocol. White matter disease by MRI alone is not an exclusion if the patient is asymptomatic.
- Other Inherited Diseases of Metabolism:
- Wolman syndrome (acid lipase deficiency)
- Niemann-Pick B patients (sphingomyelin deficiency)
- Niemann-Pick C subtype 2
- Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program: Priority will be as follows, although in circumstances in which timing is of the essence, cord blood grafts may be chosen over an unrelated graft, despite the priority listed above.
- Multidisciplinary Evaluation: Patients will be eligible for transplantation only after they are seen and evaluated by members of the Inherited Metabolic and Storage Disease Program (IMSD) team, and the team has offered transplantation to the patient/family.
Who cannot join
- Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be considered for other treatment protocols.
- Major organ dysfunction. Evidence of major organ impairment, including:
- Cardiac: left ventricular ejection fraction <40%
- Renal: serum creatinine >2.5 x normal for age
- Hepatic: total bilirubin >3 x normal, or Alanine transaminase (ALT) > 3 x normal
- Pulmonary: requirement for continuous oxygen supplementation
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- Pregnancy
- Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
- Patients >21 years of age.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota, Fairview
Minneapolis, Minnesota, 55455
About this study
Official title: Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation
The primary objective of this clinical trial is to evaluate the ability to achieve and sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of metabolism undergoing hematopoietic stem cell transplantation (HCT).
Read the detailed description
This has been an ongoing area of interest by our group at the Univ. of Minnesota, but this is a new protocol to take the place of several older protocols. While survival has been very good on the prior protocols over the past decade, incomplete engraftment has remained somewhat problematic. Therefore, we have modified the preparative regimen somewhat to increase engraftment by replacing anti-thymocyte globulin (ATG) with Campath-1H, a drug that is more immune suppressive. In addition, we have modified the supportive care regimen. Based on this, we will monitor levels of an anti-oxidant therapy (N-acetylcysteine) and biomarkers of inflammation and oxidative stress for the families that consent to these research studies.
- Conditions
- Hurler's Syndrome, Maroteaux-Lamy Syndrome, Sly Syndrome, Alpha Mannosidosis, Fucosidosis, Aspartylglucosaminuria
- Being tested
- Stem Cell Transplantation, Cyclophosphamide, Campath-1H, Busulfan
- Keywords
- Inborn errors of metabolism, Sphingolipidoses, Recessive Leukodystrophies- GLD, Krabbe disease, MLD, Peroxisomal Disorders, Wolman syndrome, Niemann-Pick B patients, Niemann-Pick C subtype 2
- Medical subject headings
- Mucopolysaccharidosis I, Mucopolysaccharidosis VI, Mucopolysaccharidosis VII, alpha-Mannosidosis, Fucosidosis, Aspartylglucosaminuria, Sphingolipidoses, Leukodystrophy, Globoid Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem Cell TransplantationProcedure or surgery
Also called Bone Marrow Transplant, cord blood transplant
The purpose of hematopoietic stem cell transplantation is to introduce blood producing cells from a normal donor. These cells can either provide what is missing in the body to the other cells, or can change the body's immune response to the substances that have accumulated in the body. These normal hematopoietic stem 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). The new donor cells repopulate the blood and bone marrow system and enter the organs of the body, including the brain. Wherever these cells go, they will produce the needed enzyme.
CyclophosphamideDrug
Also called Cytoxan
Days before Transplant Drug Frequency
- 4 Cyclophosphamide Once, given over 2 hours
- 3 Cyclophosphamide Once, given over 2 hours
- 2 Cyclophosphamide Once, given over 2 hours
- 1 Cyclophosphamide Once, given over 2 hours
Campath-1HDrug
Also called Alemtuzamab
Days before Transplant Drug Frequency
12 Campath-1H Once, given over 2 hours
11 Campath-1H Once, given over 2 hours
10 Campath-1H Once, given over 2 hours
BusulfanDrug
Also called Busulfex
Days before Transplant Drug Frequency
9 Busulfan Four times per day
8 Busulfan Four times per day
7 Busulfan Four times per day
6 Busulfan Four times per day
| Study group | Role | What they receive |
|---|---|---|
| Intent-to-Treat | Experimental | All patients treated with study regimen. Receives: Procedure: Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Campath-1H; Drug: Busulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Achieving Engraftment
Rate of successful engraftment - patients who achieved and sustained donor engraftment; donor chimerism by day 100 of at least 90% after undergoing hematopoietic stem cell transplantation.
Measured: Day 100
Secondary outcomes (1)
Overall Survival
Number of patients alive at timepoints.
Measured: Day 100, 1 Year, 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2008 (estimated)
- Study startMar 2008
- Primary completionFeb 2010
- Study completionFeb 2010
Why it stopped: Replaced by another study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hurler's SyndromeStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Orchard, MD, Principal investigator, University of Minnesota Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00668564
- Sponsor's protocol ID
- MT2008-02
- Other IDs
- 0801M25202
- Status last verified
- Dec 2017
- First submitted
- 25 Apr 2008
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 21586746
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT00668564
- Acronym / sponsor ID
- MT2008-02
- Conditions
- Hurler's Syndrome, Maroteaux-Lamy Syndrome, Sly Syndrome, Alpha Mannosidosis, Fucosidosis, Aspartylglucosaminuria
- Keywords
- Inborn errors of metabolism, Sphingolipidoses, Recessive Leukodystrophies- GLD, Krabbe disease, MLD, Peroxisomal Disorders, Wolman syndrome, Niemann-Pick B patients, Niemann-Pick C subtype 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Replaced by another study
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Mar 2008
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 29 Apr 2008 (estimated)
- Results
- Posted 13 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this clinical trial is to evaluate the ability to achieve and sustain donor engraftment in patients with lysosomal and peroxisomal inborn errors of metabolism undergoing hematopoietic stem cell transplantation (HCT).
Detailed description
This has been an ongoing area of interest by our group at the Univ. of Minnesota, but this is a new protocol to take the place of several older protocols. While survival has been very good on the prior protocols over the past decade, incomplete engraftment has remained somewhat problematic. Therefore, we have modified the preparative regimen somewhat to increase engraftment by replacing anti-thymocyte globulin (ATG) with Campath-1H, a drug that is more immune suppressive. In addition, we have modified the supportive care regimen. Based on this, we will monitor levels of an anti-oxidant therapy (N-acetylcysteine) and biomarkers of inflammation and oxidative stress for the families that consent to these research studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intent-to-Treat | Experimental | Procedure: Stem Cell Transplantation, Drug: Cyclophosphamide, Drug: Campath-1H, Drug: BusulfanAll patients treated with study regimen. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Mucopolysaccharidosis (MPS) Disorders:
- Glycoprotein metabolic disorders:
- Sphingolipidoses and Recessive Leukodystrophies: Presymptomatic patients with globoid cell leukodystrophy (GLD, also known as Krabbe disease) and metachromatic leukodystrophy (MLD) will be eligible for treatment on this protocol. White matter disease by magnetic resonance imaging (MRI) alone is not an exclusion if the patient is asymptomatic.
- Peroxisomal Disorders: Presymptomatic patients with inherited peroxisomal disorders associated with of very long chain fatty acids (VLCFA) elevation, identified by family history or laboratory testing (including neonatal screening), are eligible for this protocol. White matter disease by MRI alone is not an exclusion if the patient is asymptomatic.
- Other Inherited Diseases of Metabolism:
Key exclusion criteria (9 listed)
- Symptomatic patients with peroxisomal or lysosomal disorders are excluded but may be considered for other treatment protocols.
- Major organ dysfunction. Evidence of major organ impairment, including:
- Pregnancy
- Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
- Patients >21 years of age.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stem Cell TransplantationAlso: Bone Marrow Transplant, cord blood transplantThe purpose of hematopoietic stem cell transplantation is to introduce blood producing cells from a normal donor. These cells can either provide what is missing in the body to the other cells, or can change the body's immune response to the substances that have accumulated in the body. These normal hematopoietic stem 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). The new donor cells repopulate the blood and bone marrow system and enter the organs of the body, including the brain. Wherever these cells go, they will produce the needed enzyme. | Procedure or surgery | Intent-to-Treat |
| CyclophosphamideAlso: CytoxanDays before Transplant Drug Frequency * 4 Cyclophosphamide Once, given over 2 hours * 3 Cyclophosphamide Once, given over 2 hours * 2 Cyclophosphamide Once, given over 2 hours * 1 Cyclophosphamide Once, given over 2 hours | Drug | Intent-to-Treat |
| Campath-1HAlso: AlemtuzamabDays before Transplant Drug Frequency 12 Campath-1H Once, given over 2 hours 11 Campath-1H Once, given over 2 hours 10 Campath-1H Once, given over 2 hours | Drug | Intent-to-Treat |
| BusulfanAlso: BusulfexDays before Transplant Drug Frequency 9 Busulfan Four times per day 8 Busulfan Four times per day 7 Busulfan Four times per day 6 Busulfan Four times per day | Drug | Intent-to-Treat |
Primary outcome
Number of Patients Achieving Engraftment
Time frame: Day 100
Rate of successful engraftment - patients who achieved and sustained donor engraftment; donor chimerism by day 100 of at least 90% after undergoing hematopoietic stem cell transplantation.
1 secondary outcome
Overall Survival
Time frame: Day 100, 1 Year, 3 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21586746Miller 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Orchard, MD principal investigator
University of Minnesota Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Stem Cell Transplantation, Cyclophosphamide and Campath-1H in people with Hurler's Syndrome and Maroteaux-Lamy Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Achieving Engraftment (time frame: Day 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00668564, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2017.