Mucopolysaccharidosis IPhase 2NCT00176917

Stem Cell Transplantation for Hurler

A Phase 2 study testing Stem Cell Transplant and Busulfan, Cyclophosphamide, ATG in people with Mucopolysaccharidosis I and Mucopolysaccharidosis VI, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for Hurler syndrome, Maroteaux Lamy syndrome, Mannosidosis, or I-cell disease. Read more about this study

Who is it for?: Any age
Conditions the study is for: Mucopolysaccharidosis I, Mucopolysaccharidosis VI, Mannosidosis
What is being tested?: Stem Cell Transplant and Busulfan, Cyclophosphamide, ATG
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 41 participants
Where: 1 siteUnited States
Study dates: May 1999to May 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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Patients with Mucopolysaccharidosis, type I (e.g., Hurler syndrome), Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or mismatched (at 1 antigen) related marrow, PBSC, or cord blood donor.
Patients with Mucopolysaccharidosis, type I, Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or HLA-1 antigen mismatched unrelated marrow, PBSC, or HLA-0-2 antigen mismatched umbilical cord blood donor.
Patients with MPS type I, Maroteaux Lamy Syndrome (MPS VI), or mucolipidosis type II (I-cell disease) will have a mental developmental index within two standard deviations of the normal mean, as best as can be determined using Bayley scales of infant development or other standardized testing, recognizing that these may be affected by speech and/or hearing impairment.
Adequate organ function:
Cardiac: ejection fraction >40%; no decompensated congestive heart failure or uncontrolled arrhythmia
Renal: serum creatinine <2.0 mg/dl
Hepatic: total bilirubin <3x Upper limits of normal transaminases < 5.0 x Upper limits of normal
Signed consent.

Who cannot join

Presence of major organ dysfunction (see above)
Pregnancy
Evidence of HIV infection or known HIV positive serology
Patients or parents are psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance
Patients >50 kg may be at risk for having cell doses below the goal of ≥ 10 x 106 CD 34 cells/kg and therefore will not be eligible to receive unrelated PBSCs.

Trial locations and contacts

1 site in 1 country.

United States1 site

Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)

Read the detailed description

Prior to transplantation, subjects will receive Busulfan intravenously (IV) via the Hickman line four times daily for 4 days, Cyclophosphamide intravenously via the Hickman line once a day for 4 days, and Anti-Thymocyte Globulin IV via the Hickman line twice daily for three days before the transplant. These three drugs are being given to subjects to help the new marrow "take" and grow.

On the day of transplantation, the donor's hematopoietic cells will be transfused via central venous catheter.

After hematopoietic cell transplant, subjects will then receive two drugs, cyclosporin and either methylprednisolone or Mycophenolate Mofetil (MMF). Cyclosporin and methylprednisolone or MMF are given to help prevent the complication of graft-versus-host disease and to decrease the chance that the new donor cells will be rejected.

Conditions: Mucopolysaccharidosis I, Mucopolysaccharidosis VI, Mannosidosis, Mucolipidosis Type II (I-cell Disease)
Being tested: Stem Cell Transplant, Busulfan, Cyclophosphamide, ATG
Keywords: stem cell transplant, storage disease, errors of metabolism
Medical subject headings: Mucopolysaccharidosis I, Mucopolysaccharidosis VI, Mannosidase Deficiency Diseases, Mucolipidoses

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Stem Cell TransplantProcedure or surgery
Also called Bone Marrow Transplant
The purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains the enzyme able to get rid of the substances that have accumulated in the body of patients with storage diseases. Hematopoietic 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).
Busulfan, Cyclophosphamide, ATGDrug
Also called Busulfex, Cytoxan, Thymoglobulin
Prior to transplantation, subjects will receive BUSULFAN intravenously (IV) via the Hickman line twice daily for 4 days, CYCLOPHOSPHAMIDE intravenously via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV via the Hickman line twice daily for three days before the transplant. These three drugs are being given to help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.

Study groups in NCT00176917
Study group	Role	What they receive
Treatment Arm	Experimental	All patients treated with chemotherapy and transplantation. Receives: Procedure: Stem Cell Transplant; Drug: Busulfan, Cyclophosphamide, ATG

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Percentage of Donor Cells in Study Population (Chimerism).
Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).
Measured: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year

Secondary outcomes (3)

Number of Patients Surviving on Study
Number of patients surviving (alive) at specified timepoints.
Measured: at 100 days, 1 year, and 3 years post transplant
Number of Patients Who Failed Engraftment.
Toxicity (undesireable effect) of hematologic donor cell engraftment is determined by failure to engraft at Day 42.
Measured: Day 42 Post Transplant
Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).
Toxicity (undesireable effect) of this stem cell transplant preparative regimen due to acute graft-versus-host disease.
Measured: Day 100 Post Transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 1999May 2010

First posted15 Sep 2005 (estimated)
Study startMay 1999
Primary completionMay 2008
Study completionMay 2010

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.
Other trials for Mucopolysaccharidosis IStudies of the same condition, open and under way.
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: 41 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00176917
Sponsor's protocol ID: UMN-MT1999-07
Other IDs: 0104M93821
Status last verified: Dec 2017
First submitted: 12 Sep 2005
Last updated: 28 Dec 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
RecruitingPhase 1/2
A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)
Mucopolysaccharidosis IIIB
Not yet recruitingPhase 1/2
Single Injection of rAAV9-CMV-hNAGLUop Gene for Patients With Mucopolysaccharidosis (MPS) IIIB
Sanfilippo Syndrome (MPS III)

All Mucopolysaccharidosis I trials

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: Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)
ClinicalTrials.gov ID: NCT00176917
Acronym / sponsor ID: UMN-MT1999-07
Conditions: Mucopolysaccharidosis I, Mucopolysaccharidosis VI, Mannosidosis, Mucolipidosis Type II (I-cell Disease)
Keywords: stem cell transplant, storage disease, errors of metabolism
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 41 participants (actual)
Lead sponsor: Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
Study start: May 1999
Primary completion: May 2008 (actual)
Study completion: May 2010 (actual)
First posted: 15 Sep 2005 (estimated)
Results: Posted 4 Sep 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

On the day of transplantation, the donor's hematopoietic cells will be transfused via central venous catheter.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment Arm	Experimental	Procedure: Stem Cell Transplant, Drug: Busulfan, Cyclophosphamide, ATGAll patients treated with chemotherapy and transplantation.

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

Patients with Mucopolysaccharidosis, type I (e.g., Hurler syndrome), Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or mismatched (at 1 antigen) related marrow, PBSC, or cord blood donor.
Patients with Mucopolysaccharidosis, type I, Maroteaux-Lamy syndrome (MPS VI), Alpha Mannosidosis, or mucolipidosis type II (I-cell disease) who have an HLA-identical or HLA-1 antigen mismatched unrelated marrow, PBSC, or HLA-0-2 antigen mismatched umbilical cord blood donor.
Patients with MPS type I, Maroteaux Lamy Syndrome (MPS VI), or mucolipidosis type II (I-cell disease) will have a mental developmental index within two standard deviations of the normal mean, as best as can be determined using Bayley scales of infant development or other standardized testing, recognizing that these may be affected by speech and/or hearing impairment.
Adequate organ function:
Cardiac: ejection fraction >40%; no decompensated congestive heart failure or uncontrolled arrhythmia

Key exclusion criteria (5 listed)

Presence of major organ dysfunction (see above)
Pregnancy
Evidence of HIV infection or known HIV positive serology
Patients or parents are psychologically incapable of undergoing BMT with associated strict isolation or documented history of medical non-compliance
Patients >50 kg may be at risk for having cell doses below the goal of ≥ 10 x 106 CD 34 cells/kg and therefore will not be eligible to receive unrelated PBSCs.

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 TransplantAlso: Bone Marrow TransplantThe purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains the enzyme able to get rid of the substances that have accumulated in the body of patients with storage diseases. Hematopoietic 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).	Procedure or surgery	Treatment Arm
Busulfan, Cyclophosphamide, ATGAlso: Busulfex, Cytoxan, ThymoglobulinPrior to transplantation, subjects will receive BUSULFAN intravenously (IV) via the Hickman line twice daily for 4 days, CYCLOPHOSPHAMIDE intravenously via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV via the Hickman line twice daily for three days before the transplant. These three drugs are being given to help the new marrow "take" and grow. METHYLPREDNISOLONE will be given as a pre-medication for the ATG.	Drug	Treatment Arm

Primary outcome

Mean Percentage of Donor Cells in Study Population (Chimerism).
Time frame: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year
Donor-derived engraftment determined by restriction fragment length polymorphism (RFLP).

3 secondary outcomes

Number of Patients Surviving on Study
Time frame: at 100 days, 1 year, and 3 years post transplant
Number of Patients Who Failed Engraftment.
Time frame: Day 42 Post Transplant
Number of Patients With Grade III-IV Acute Graft-versus-host Disease (aGVHD).
Time frame: Day 100 Post Transplant

Results and safety

Results posted to the registry on 4 Sep 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Transplant Patients	41	41

Primary outcome: Mean Percentage of Donor Cells in Study Population (Chimerism).

Time frame: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year. Mean (Standard Deviation). Unit: Percentage

Measure	Transplant Patients n = 41
21 Days Post Transplant	85.8 (28.4)
42 Days Post Transplant	73.2 (31.6)
60 Days Post Transplant	84.6 (27.9)
100 Days Post Transplant	81.1 (26.8)
6 Months Post Transplant	81.6 (29.6)
1 Year Post Transplant	91.5 (18.8)

Population analysed: Day 21 (24 patients included), Day 42 (15 pts), Day 60 (29 pts), Day 100 (25 pts), 6 Months (18 pts), 1 Year (16 pts).

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Transplant Patients	0 of 41 (0%)	0 of 41 (0%)	Not reported

Limitations and caveats (from the sponsor): Based on variability in age, diagnosis and condition of these patients, the data on enzyme levels and neuropsych testing is extremely difficult to report. See Secondary Outcome Measures #3 and #4; no other adverse events were collected.

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.

Related trials for Mucopolysaccharidosis I

RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 2/3
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
MPS IIIA, Sanfilippo Syndrome
RecruitingPhase 1/2
A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)
Mucopolysaccharidosis IIIB
Not yet recruitingPhase 1/2
Single Injection of rAAV9-CMV-hNAGLUop Gene for Patients With Mucopolysaccharidosis (MPS) IIIB
Sanfilippo Syndrome (MPS III)

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

Masonic Cancer Center, University of Minnesota

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 8 inclusion and 5 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: finished, 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 4 Sep 2009). 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?

Mean Percentage of Donor Cells in Study Population (Chimerism). (time frame: at 21 days, 42 days, 60 days, 100 days, 6 months, and 1 year). 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 NCT00176917.

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.