AdrenoleukodystrophyPhase 2/3NCT00176904
Stem Cell Transplant for Inborn Errors of Metabolism
A Phase 2/3 study testing Stem Cell Transplant and Busulfan, Cyclophosphamide, Antithymocyte Globulin in people with Adrenoleukodystrophy and Metachromatic Leukodystrophy, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
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 an inherited metabolic storage disease. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Adrenoleukodystrophy, Metachromatic Leukodystrophy, Globoid Cell Leukodystrophy
- What is being tested?
- Stem Cell Transplant and Busulfan, Cyclophosphamide, Antithymocyte Globulin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1995to Jun 2010
- Phase
- Phase 2/3
- 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 adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy, Gaucher's disease, Fucosidosis, Wolman disease, Niemann-Pick disease and Batten disease (CLN3) who have a human leukocyte antigen (HLA)-identical or haplotype mismatched (at 1-3 antigens) related marrow, or umbilical cord blood donor. One or two umbilical cord blood (UCB) units may be used.
- Patients with GM1 gangliosidosis, Tay Sachs disease or Sandhoff disease who have a HLA-identical or 1 antigen mismatched related or unrelated donor, or suitably matched umbilical cord blood unit(s). One or two UCB units may be used.
- Patients with adrenoleukodystrophy must have magnetic resonance imaging (MRI) findings, neurological and neuropsychometric function consistent with the diagnosis, and for boys with parietal-occipital dysmyelination a performance intelligence quotient (IQ) ≥80. In cases, when the performance IQ is not ≥80, the protocol committee may recommend transplant if the patient's clinical condition and neuropsychometric status are deemed to be acceptable based upon consideration of such factors as age at onset of cerebral disease, magnitude of change in performance IQ and neurologic deficits.
- Patients with arylsulfatase A deficiency (Metachromatic Leukodystrophy) must have either the presymptomatic late infantile, juvenile or adult form of the disease and must have acceptable neurological and neuropsychometric function.
- Patients with galactocerebrosidase deficiency (Globoid Cell Leukodystrophy) must have acceptable neurological and neuropsychometric function.
- Patients with acid lipase deficiency (Wolman disease) must have a liver biopsy that documents no evidence of hepatic cirrhosis, and acceptable neurological and neuropsychometric function.
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- Patients with fucosidase deficiency (Fucosidosis) must have acceptable neurological and neuropsychometric function.
- Patients with glucocerebrosidase deficiency (Gaucher's Disease) must have acceptable neurologic and neuropsychometric function.
- Patients with Batten's disease (CLN3) must have acceptable Neurological and neuropsychometric function.
- Absence of major organ dysfunction. Organ evaluation results as follows:
- Cardiac: ejection fraction >30%
- Renal: serum creatinine <2x normal or creatinine clearance 60 mL/min.
- Hepatic: total bilirubin <2x normal and Aspartate aminotransferase (AST) <2x normal
- Signed consent.
Who cannot join
- Patients with symptomatic late infantile form of metachromatic leukodystrophy.
- Patients with symptomatic infantile globoid leukodystrophy.
- Note: Patients with Hurler syndrome, mucopolysaccharidosis (MPS) VI, or Mannosidosis disease are no longer eligible for this protocol, but can be transplanted under protocol MT 9907 (NCT00176917 - Hematopoietic Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)).
- Pregnancy
- Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
- Patients or parents are psychologically incapable of undergoing bone marrow transplant (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 10^6 CD34 cells/kg and therefore will not be eligible to receive unrelated peripheral blood stem cells (PBSCs)
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: Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Bone Marrow Transplantation
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 an inherited metabolic storage disease.
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 (ATG) intravenously (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
- Adrenoleukodystrophy, Metachromatic Leukodystrophy, Globoid Cell Leukodystrophy, Gaucher's Disease, Fucosidosis, Wolman Disease
- Being tested
- Stem Cell Transplant, Busulfan, Cyclophosphamide, Antithymocyte Globulin
- Keywords
- Inborn errors, Storage disease, errors of metabolism, stem cell transplant
- Medical subject headings
- Adrenoleukodystrophy, Leukodystrophy, Metachromatic, Leukodystrophy, Globoid Cell, Gaucher Disease, Fucosidosis, Wolman Disease, Niemann-Pick Diseases, Neuronal Ceroid-Lipofuscinoses
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 an 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, Antithymocyte GlobulinDrug
Also called Busulfex, Cytoxan, ATG
Subjects will receive BUSULFAN intravenously (IV)- patients < or= 12 kg 1.1 mg/kd/dose IV every 6 hours for 16 doses; patients > 12kg 0.8 mg/kg/dose IV every 6 hours for 16 doses - via the Hickman line four times daily for 4 days, CYCLOPHOSPHAMIDE intravenously (50 mg/kg/day IV over 2 hours) via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV (15 mg/kg/day over 2 hours) 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 group | Role | What they receive |
|---|---|---|
| Treated Patients | Experimental | All patients treated with protocol regimen (chemotherapy and surgery). Receives: Procedure: Stem Cell Transplant; Drug: Busulfan, Cyclophosphamide, Antithymocyte Globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Number of patients alive at designated timepoints after transplant.
Measured: 100 Days, 1 Year and 3 Years
Secondary outcomes (4)
Overall Donor Engraftment
Number of patients with full donor chimerism (state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease) by Day 100 post-transplant of at least 90%.
Measured: Day 100
Number of Patients With Grade II-IV Acute Graft-Versus-Host Disease
Number of patients who exhibited acute graft-versus-host disease by Day 100 post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Grade I=mild, Grade II=moderate, Grade III=severe, Grade IV=life threatening.
Measured: Day 100
Number of Patients With Grade III-IV Acute Graft-Versus-Host Disease
Number of patients who exhibited acute graft-versus-host disease by Day 100 post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Grade I=mild, Grade II=moderate, Grade III=severe, Grade IV=life threatening.
Measured: Day 100
Number of Patients With Chronic Graft-Versus-Host Disease
Number of patients who exhibited chronic graft-versus-host disease by 1 Year post transplant. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Chronic GVHD is an extension of this syndrome.
Measured: 1 Year Post Transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startJan 1995
- Primary completionJun 2010
- Study completionJun 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AdrenoleukodystrophyStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 135 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
- NCT00176904
- Sponsor's protocol ID
- MT1995-01
- 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
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 Bone Marrow Transplantation
- ClinicalTrials.gov ID
- NCT00176904
- Acronym / sponsor ID
- MT1995-01
- Conditions
- Adrenoleukodystrophy, Metachromatic Leukodystrophy, Globoid Cell Leukodystrophy, Gaucher's Disease, Fucosidosis, Wolman Disease
- Keywords
- Inborn errors, Storage disease, errors of metabolism, stem cell transplant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Jan 1995
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 10 Jun 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 an inherited metabolic storage disease.
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 (ATG) intravenously (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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treated Patients | Experimental | Procedure: Stem Cell Transplant, Drug: Busulfan, Cyclophosphamide, Antithymocyte GlobulinAll patients treated with protocol regimen (chemotherapy and surgery). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy, Gaucher's disease, Fucosidosis, Wolman disease, Niemann-Pick disease and Batten disease (CLN3) who have a human leukocyte antigen (HLA)-identical or haplotype mismatched (at 1-3 antigens) related marrow, or umbilical cord blood donor. One or two umbilical cord blood (UCB) units may be used.
- Patients with GM1 gangliosidosis, Tay Sachs disease or Sandhoff disease who have a HLA-identical or 1 antigen mismatched related or unrelated donor, or suitably matched umbilical cord blood unit(s). One or two UCB units may be used.
- Patients with adrenoleukodystrophy must have magnetic resonance imaging (MRI) findings, neurological and neuropsychometric function consistent with the diagnosis, and for boys with parietal-occipital dysmyelination a performance intelligence quotient (IQ) ≥80. In cases, when the performance IQ is not ≥80, the protocol committee may recommend transplant if the patient's clinical condition and neuropsychometric status are deemed to be acceptable based upon consideration of such factors as age at onset of cerebral disease, magnitude of change in performance IQ and neurologic deficits.
- Patients with arylsulfatase A deficiency (Metachromatic Leukodystrophy) must have either the presymptomatic late infantile, juvenile or adult form of the disease and must have acceptable neurological and neuropsychometric function.
- Patients with galactocerebrosidase deficiency (Globoid Cell Leukodystrophy) must have acceptable neurological and neuropsychometric function.
Key exclusion criteria (7 listed)
- Patients with symptomatic late infantile form of metachromatic leukodystrophy.
- Patients with symptomatic infantile globoid leukodystrophy.
- Note: Patients with Hurler syndrome, mucopolysaccharidosis (MPS) VI, or Mannosidosis disease are no longer eligible for this protocol, but can be transplanted under protocol MT 9907 (NCT00176917 - Hematopoietic Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis)).
- Pregnancy
- 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 |
|---|---|---|
| Stem Cell TransplantAlso: Bone marrow transplantThe purpose of hematopoietic cell transplantation is to introduce hematopoietic cells from a normal donor that contains an 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 | Treated Patients |
| Busulfan, Cyclophosphamide, Antithymocyte GlobulinAlso: Busulfex, Cytoxan, ATGSubjects will receive BUSULFAN intravenously (IV)- patients < or= 12 kg 1.1 mg/kd/dose IV every 6 hours for 16 doses; patients > 12kg 0.8 mg/kg/dose IV every 6 hours for 16 doses - via the Hickman line four times daily for 4 days, CYCLOPHOSPHAMIDE intravenously (50 mg/kg/day IV over 2 hours) via the Hickman line once a day for 4 days, and ANTI-THYMOCYTE GLOBULIN IV (15 mg/kg/day over 2 hours) 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 | Treated Patients |
Primary outcome
Overall Survival
Time frame: 100 Days, 1 Year and 3 Years
Number of patients alive at designated timepoints after transplant.
4 secondary outcomes
Overall Donor Engraftment
Time frame: Day 100
Number of Patients With Grade II-IV Acute Graft-Versus-Host Disease
Time frame: Day 100
Number of Patients With Grade III-IV Acute Graft-Versus-Host Disease
Time frame: Day 100
Number of Patients With Chronic Graft-Versus-Host Disease
Time frame: 1 Year Post Transplant
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
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 2/3 study testing Stem Cell Transplant and Busulfan, Cyclophosphamide, Antithymocyte Globulin in people with Adrenoleukodystrophy and Metachromatic Leukodystrophy, 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 14 inclusion and 7 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 10 Jun 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?
Overall Survival (time frame: 100 Days, 1 Year and 3 Years). 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 NCT00176904, 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.