MucopolysaccharidosisPhase 2NCT01043640
Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
A Phase 2 study testing Campath-1H, Cyclophosphamide and Busulfan in people with Mucopolysaccharidosis and Hurler Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Mucopolysaccharidosis, Hurler Syndrome, Hunter Syndrome
- What is being tested?
- Campath-1H, Cyclophosphamide and Busulfan
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Jun 2017
- 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
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders
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.
- Conditions
- Mucopolysaccharidosis, Hurler Syndrome, Hunter Syndrome, Maroteaux-Lamy Syndrome, Sly Syndrome, Alpha Mannosidosis
- Being tested
- Campath-1H, Cyclophosphamide, Busulfan, Allogeneic stem cell transplantation, Cyclosporine A
- Keywords
- inherited metabolic disorders
- Medical subject headings
- Mucopolysaccharidoses, Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis VI, Mucopolysaccharidosis VII, alpha-Mannosidosis, Fucosidosis, Aspartylglucosaminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Campath-1HDrug
Also called Alemtuzumab
Administered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV)
CyclophosphamideDrug
Also called Cytoxan(R)
Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily.
BusulfanDrug
Also called Busulfex(R)
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
Allogeneic stem cell transplantationProcedure or surgery
Also called stem cell transplant
Administered > 24 hours after last dose of busulfan.
Cyclosporine ADrug
Also called CsA
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 called MMF
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.
| Study group | Role | What they receive |
|---|---|---|
| Transplant Patients | Experimental | Includes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. Receives: Drug: Campath-1H; Drug: Cyclophosphamide; Drug: Busulfan; Procedure: Allogeneic stem cell transplantation; Drug: Cyclosporine A; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 100 Post Transplant
Secondary outcomes (11)
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
Measured: Day 100 Post Transplant
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
Measured: Day 100 Post Transplant
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
Measured: Day 100 Post Transplant
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
Measured: Day 100 Post Transplant
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
Measured: Day 100 Post Transplant
Number of Patients Who Died Peri-Transplant
Peri-transplant is defined as within 100 days of transplant.
Measured: By Day 100 Post Transplant
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.
Measured: Day 28
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.
Measured: Day 42
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.
Measured: Day 100
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.
Measured: 6 months
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2010 (estimated)
- Study startDec 2009
- Primary completionJun 2015
- Study completionJun 2017
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 MucopolysaccharidosisStudies 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
- 46 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, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01043640
- Sponsor's protocol ID
- 2009LS088
- Other IDs
- MT2009-19
- Status last verified
- Sep 2017
- First submitted
- 5 Jan 2010
- Last updated
- 5 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders
- ClinicalTrials.gov ID
- NCT01043640
- Acronym / sponsor ID
- 2009LS088
- Conditions
- Mucopolysaccharidosis, Hurler Syndrome, Hunter Syndrome, Maroteaux-Lamy Syndrome, Sly Syndrome, Alpha Mannosidosis
- Keywords
- inherited metabolic disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 7 Jan 2010 (estimated)
- Results
- Posted 12 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transplant Patients | Experimental | Drug: Campath-1H, Drug: Cyclophosphamide, Drug: Busulfan, Procedure: Allogeneic stem cell transplantation, Drug: Cyclosporine A, Drug: Mycophenolate MofetilIncludes patients who received allogeneic stem cell transplantation following treatment plan of Campath-1H, cyclophosphamide, cyclosporine A, mycophenolate mofetil, and busulfan. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
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 |
|---|---|---|
| Campath-1HAlso: AlemtuzumabAdministered Days -21, -20 and -19, 0.3 mg/kg subcutaneously (SQ) or intravenously (IV) | Drug | Transplant Patients |
| CyclophosphamideAlso: Cytoxan(R)Administered days -10 through -6, 50 mg/kg/day intravenous (IV) over 2 hours - with Mesna continuous infusion or 5 times daily. | Drug | Transplant Patients |
| BusulfanAlso: Busulfex(R)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 | Drug | Transplant Patients |
| Allogeneic stem cell transplantationAlso: stem cell transplantAdministered > 24 hours after last dose of busulfan. | Procedure or surgery | Transplant Patients |
| Cyclosporine AAlso: CsA2.5 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). | Drug | Transplant Patients |
| Mycophenolate MofetilAlso: MMF15 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. | Drug | Transplant Patients |
Primary outcome
Number of Patients With Donor Derived Engraftment
Time frame: Day 100 Post Transplant
Donor derived engraftment is defined as 80 percent or greater donor cells in the recipient's bone marrow and blood cells.
11 secondary outcomes
Number of Patients With Grade 0 Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients With Grade 1 Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients With Grade 2 Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients With Grade 3 Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients With Grade 4 Graft-Versus-Host Disease (GVHD)
Time frame: Day 100 Post Transplant
Number of Patients Who Died Peri-Transplant
Time frame: By Day 100 Post Transplant
Donor Cell Chimerism Following Transplant
Time frame: Day 28
Donor Cell Chimerism Following Transplant
Time frame: Day 42
Donor Cell Chimerism Following Transplant
Time frame: Day 100
Donor Cell Chimerism Following Transplant
Time frame: 6 months
Donor Cell Chimerism Following Transplant
Time frame: One year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
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?
A Phase 2 study testing Campath-1H, Cyclophosphamide and Busulfan in people with Mucopolysaccharidosis and Hurler 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 3 inclusion and 2 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 5 Feb 2018. 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 12 May 2017). 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 With Donor Derived Engraftment (time frame: Day 100 Post Transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Feb 2018.