Lysosomal Storage DiseaseNCT01626092
Reduced-Intensity Hematopoietic Stem Cell Transplant for High Risk Lysosomal and Peroxisomal Disorders
A study testing Campath-1H, Clofarabine and Melphalan in people with Lysosomal Storage Disease and Peroxisomal Disorder, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
This study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) in patients with high-risk lysosomal and peroxisomal disorders using a novel conditioning regimen for hematopoietic cell transplantation (HCT). Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Lysosomal Storage Disease, Peroxisomal Disorder
- What is being tested?
- Campath-1H, Clofarabine and Melphalan
- 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
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jul 2012to Nov 2013
- Phase
- Interventional
- 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 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Adrenoleukodystrophy (ALD): Patients from 0-55 years of age diagnosed with ALD as determined by very long chain fatty acid testing will be eligible for this protocol if they have evidence of cerebral or cerebellar disease based on MRI testing,
- Metachromatic Leukodystrophy (MLD): Patients from 0-55 years of age diagnosed with MLD as determined by arylsulfatase A activity.
- Globoid Cell Leukodystrophy (GLD): Patients from 0-55 years of age diagnosed with GLD as determined by galactocerebrosidase activity will be eligible for this protocol
- Wolman's disease, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome, Sandhoff disease or other inherited metabolic diseases including but not limited to I-cell disease (mucolipidosis II): Patients who are determined to be sufficiently advanced or high risk based on the following reasons:
- Symptomatic disease, as based on neurologic examination or evidence of deterioration based on subsequent neuropsychologic evaluations.
- Evidence of an expected poor outcome based on genetic testing or a prior family history of aggressive disease.
Show all 13Show fewer
- Other metabolic disorders, including but not limited to I-cell disease, that are deemed to be high-risk for a poor outcome with a standard transplant regimen due to anticipated toxicity based on experience gained at the University of Minnesota or other centers.
- Donor Availability
- Transplantation using sufficiently matched related donors (such as matched siblings) or unrelated donors will be considered. Both granulocyte-colony stimulating factor (G-CSF) stimulated peripheral blood grafts and bone marrow grafts will be considered, although bone marrow will be the priority.
- Cord blood grafts, both related and unrelated, are also eligible. As this protocol will use a reduced intensity regimen, this protocol will use the current recommendations of the University of Minnesota for choosing cord blood grafts. If a single cord blood unit cell dose is insufficient, double cord transplantation should be considered if sufficiently matched cord blood units are available. The priority of choosing cord blood donors is based on the current institutional recommendations.
- Exclusion of Metabolic Disorder Carrier Status from related donor and unrelated cord blood grafts as appropriate for primary disease.
- Adequate Organ Function - Measured within 30 days of study enrollment
- Signed consent
Who cannot join
- Inability to receive total body irradiation (TBI) with marrow boosting per protocol guidelines as determined by the Radiation Oncologist
- Pregnant - Menstruating females must have a negative serum pregnancy test within 14 days of treatment start.
- Advanced Disease Exclusion: Following evaluation, if a consensus of the members of the Inherited Metabolic and Storage Disease Program is that a patient is too advanced to benefit in a measurable and meaningful way from transplant, this will be communicated to the family, and transplant will not be offered.
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 High Risk, Inherited Lysosomal and Peroxisomal Disorders by Reduced-Intensity Hematopoietic Cell Transplantation and Low-Dose Total Body Irradiation With Marrow Boosting by Volumetric-Modulated Arc Therapy (VMAT)
This study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) in patients with high-risk lysosomal and peroxisomal disorders using a novel conditioning regimen for hematopoietic cell transplantation (HCT). After a reduced-intensity conditioning regimen using volumetric-modulated arc therapy (VMAT)-delivered low-dose total body irradiation (TBI) with highly conformal marrow boosting, patients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability.
Read the detailed description
The conditioning regimen consists of alemtuzumab (Campath-1H), clofarabine, melphalan, and VMAT-delivered low-dose TBI with boosted marrow irradiation. Additional graft-versus-host disease prophylaxis consists of mycophenolate mofetil and cyclosporine.
- Conditions
- Lysosomal Storage Disease, Peroxisomal Disorder
- Being tested
- Campath-1H, Clofarabine, Melphalan, Total Body Irradiation with Marrow Boosting, Hematopoietic stem cell transplantation
- Keywords
- bone marrow transplantation, reduced intensity conditioning, Adrenoleukodystrophy, Metachromatic Leukodystrophy, Globoid Cell Leukodystrophy, Wolman's disease, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome, Sandhoff disease, inherited metabolic, I-cell disease, mucolipidosis II
- Medical subject headings
- Lysosomal Storage Diseases, Peroxisomal Disorders, Adrenoleukodystrophy, Leukodystrophy, Metachromatic, Leukodystrophy, Globoid Cell, Wolman Disease, Gangliosidosis, GM1, Tay-Sachs Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Campath-1HDrug
Also called alemtuzumab-1H
A daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8.
ClofarabineDrug
Also called Clolar
A daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9,
-8, -7, -6, and -5.
MelphalanDrug
Also called Alkeran
A single dose of 140 mg/m2 will be given IV on day -4 over 15 minutes.
Total Body Irradiation with Marrow BoostingRadiation
Also called Volumetric-Modulated Arc Therapy (VMAT)
- Dose to total body 200 cGy in single dose
- Dose to bone marrow of the following bones 800 cGy in 5 divided daily fractions (160 cGy x 5 doses ). Treated with up to 3 abutting VMAT photon arcs from top of head to maximum inferior border.
Hematopoietic stem cell transplantationBiological
Patients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability.
Cyclosporine ADrug
Also called CsA
Patients will receive CsA therapy beginning on day -3. Dosing of CsA will be 2.5 mg/kg/dose IV; if the recipient body weight is <40 kg, dosing will be 3 times daily, and if > 40 kg, twice daily. An attempt will be made to maintain a trough cyclosporine level of 200 mg/L to 400 mg/L.
Also called MMF
Patients will receive mycophenolate mofetil (MMF) therapy beginning on day -3. Dosing of MMF will be 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg/dose three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously.
| Study group | Role | What they receive |
|---|---|---|
| Intent-To-Treat Patients | Experimental | Patients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor. Receives: Drug: Campath-1H; Drug: Clofarabine; Drug: Melphalan; Radiation: Total Body Irradiation with Marrow Boosting; Biological: Hematopoietic 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.
Donor (Allogeneic) Hematopoietic Engraftment
Number of patients who achieve hematopoietic engraftment - assessment of nucleated peripheral blood cells for donor (allogeneic) chimerism following this reduced-intensity HCT.
Measured: Day 100 Following Hematopoietic Cell Transplant (HCT)
Secondary outcomes (2)
Transplant-Related Mortality
Incidence of death due to complications of HCT following this reduced-intensity conditioning regimen.
Measured: Day 100 following HCT
Neurologic Outcomes
Depending upon underlying primary disease, a combination of evaluative tools (e.g. brain magnetic resonance imaging (MRI), clinical neurologic exam, neuropsychologic testing, electromyography) will be applied for assessment of neurologic function and how it may be affected by this reduced-intensity HCT regimen.
Measured: Changes from Baseline, Days 30, 60, 100, Year 1, Year 2, Year 3 Following HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2012 (estimated)
- Study start11 Jul 2012
- Primary completionNov 2013
- Study completionNov 2013
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 Lysosomal Storage DiseaseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Weston Miller, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01626092
- Sponsor's protocol ID
- 2011LS147
- Other IDs
- MT2011-24
- Status last verified
- Dec 2017
- First submitted
- 20 Jun 2012
- Last updated
- 5 Dec 2017
- 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 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of High Risk, Inherited Lysosomal and Peroxisomal Disorders by Reduced-Intensity Hematopoietic Cell Transplantation and Low-Dose Total Body Irradiation With Marrow Boosting by Volumetric-Modulated Arc Therapy (VMAT)
- ClinicalTrials.gov ID
- NCT01626092
- Acronym / sponsor ID
- 2011LS147
- Conditions
- Lysosomal Storage Disease, Peroxisomal Disorder
- Keywords
- bone marrow transplantation, reduced intensity conditioning, Adrenoleukodystrophy, Metachromatic Leukodystrophy, Globoid Cell Leukodystrophy, Wolman's disease, GM1 gangliosidosis, Tay Sachs disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 11 Jul 2012 (actual)
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 22 Jun 2012 (estimated)
- Results
- Posted 11 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to test the ability to achieve donor hematopoietic engraftment while maintaining low rates of transplant-related mortality (TRM) in patients with high-risk lysosomal and peroxisomal disorders using a novel conditioning regimen for hematopoietic cell transplantation (HCT). After a reduced-intensity conditioning regimen using volumetric-modulated arc therapy (VMAT)-delivered low-dose total body irradiation (TBI) with highly conformal marrow boosting, patients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability.
Detailed description
The conditioning regimen consists of alemtuzumab (Campath-1H), clofarabine, melphalan, and VMAT-delivered low-dose TBI with boosted marrow irradiation. Additional graft-versus-host disease prophylaxis consists of mycophenolate mofetil and cyclosporine.
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 Patients | Experimental | Drug: Campath-1H, Drug: Clofarabine, Drug: Melphalan, Radiation: Total Body Irradiation with Marrow Boosting, Biological: Hematopoietic stem cell transplantation, Drug: Cyclosporine A, Drug: Mycophenolate mofetilPatients with high-risk lysosomal and peroxisomal disorders treated with preparative regimen (Campath-1H 0.3 mg/kg intravenous (IV) on days -12 through -8, clofarabine 40 mg/m^2 IV on days -9 through -5, melphalan 140 mg/m^2 IV on day -4 and Total Body Irradiation with Marrow Boosting [ first dose of 200 cGy single dose; 5 doses of 160cGy for marrow boosting - 1000cGy cumulative exposure] by Volumetric-Modulated Arc Therapy [VMAT] on days -3 through -1). Hematopoietic stem cell transplantation will be infused on Day 0. Post-transplant immunosuppression to follow: Mycophenolate mofetil (MMF) begin day -3 and continue to day +30 or 7 days after engraftment, whichever is later; Cyclosporine A (CsA) begin day -3 and then taper at day +100 if related donor, day +180 for unrelated donor. |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Adrenoleukodystrophy (ALD): Patients from 0-55 years of age diagnosed with ALD as determined by very long chain fatty acid testing will be eligible for this protocol if they have evidence of cerebral or cerebellar disease based on MRI testing,
- Metachromatic Leukodystrophy (MLD): Patients from 0-55 years of age diagnosed with MLD as determined by arylsulfatase A activity.
- Globoid Cell Leukodystrophy (GLD): Patients from 0-55 years of age diagnosed with GLD as determined by galactocerebrosidase activity will be eligible for this protocol
- Wolman's disease, GM1 gangliosidosis, Tay Sachs disease, Sanfilippo syndrome, Sandhoff disease or other inherited metabolic diseases including but not limited to I-cell disease (mucolipidosis II): Patients who are determined to be sufficiently advanced or high risk based on the following reasons:
- Donor Availability
Key exclusion criteria (3 listed)
- Inability to receive total body irradiation (TBI) with marrow boosting per protocol guidelines as determined by the Radiation Oncologist
- Pregnant - Menstruating females must have a negative serum pregnancy test within 14 days of treatment start.
- Advanced Disease Exclusion: Following evaluation, if a consensus of the members of the Inherited Metabolic and Storage Disease Program is that a patient is too advanced to benefit in a measurable and meaningful way from transplant, this will be communicated to the family, and transplant will not be offered.
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: alemtuzumab-1HA daily dose of 0.3 mg/kg IV over 2 hours will be administered on days - 12, -11, -10, -9, and -8. | Drug | Intent-To-Treat Patients |
| ClofarabineAlso: ClolarA daily dose of 40 mg/m2 will be administered IV over 2 hours on days -9, -8, -7, -6, and -5. | Drug | Intent-To-Treat Patients |
| MelphalanAlso: AlkeranA single dose of 140 mg/m2 will be given IV on day -4 over 15 minutes. | Drug | Intent-To-Treat Patients |
| Total Body Irradiation with Marrow BoostingAlso: Volumetric-Modulated Arc Therapy (VMAT)1. Dose to total body 200 cGy in single dose 2. Dose to bone marrow of the following bones 800 cGy in 5 divided daily fractions (160 cGy x 5 doses ). Treated with up to 3 abutting VMAT photon arcs from top of head to maximum inferior border. | Radiation | Intent-To-Treat Patients |
| Hematopoietic stem cell transplantationPatients will be transplanted using either a related or unrelated allograft. The cell source may be marrow, peripheral blood or cord blood based on donor availability. | Biological | Intent-To-Treat Patients |
| Cyclosporine AAlso: CsAPatients will receive CsA therapy beginning on day -3. Dosing of CsA will be 2.5 mg/kg/dose IV; if the recipient body weight is <40 kg, dosing will be 3 times daily, and if > 40 kg, twice daily. An attempt will be made to maintain a trough cyclosporine level of 200 mg/L to 400 mg/L. | Drug | Intent-To-Treat Patients |
| Mycophenolate mofetilAlso: MMFPatients will receive mycophenolate mofetil (MMF) therapy beginning on day -3. Dosing of MMF will be 1 gram three times daily (total daily dose 3 grams/day) if the recipient is >50 kg, or 15 mg/kg/dose three times daily if the recipient is ≤50 kg. The same dosage is used orally or intravenously. | Drug | Intent-To-Treat Patients |
Primary outcome
Donor (Allogeneic) Hematopoietic Engraftment
Time frame: Day 100 Following Hematopoietic Cell Transplant (HCT)
Number of patients who achieve hematopoietic engraftment - assessment of nucleated peripheral blood cells for donor (allogeneic) chimerism following this reduced-intensity HCT.
2 secondary outcomes
Transplant-Related Mortality
Time frame: Day 100 following HCT
Neurologic Outcomes
Time frame: Changes from Baseline, Days 30, 60, 100, Year 1, Year 2, Year 3 Following HCT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Lysosomal Storage Disease
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Natural History of Glycosphingolipid Storage Disorders and Glycoprotein Disorders
Neurological Regression, Myoclonus
RecruitingObservational study
Parkinson's Disease in Type 1 Gaucher Disease
Parkinson Disease (PD), Type 1 Gaucher Disease
RecruitingObservational study
Oxidative Stress and Inflammatory Biomarkers in Gaucher Disease
Gaucher Disease Type I, Oxidative Stress
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.
Weston Miller, 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 study testing Campath-1H, Clofarabine and Melphalan in people with Lysosomal Storage Disease and Peroxisomal Disorder, 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 13 inclusion and 3 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 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Oct 2016). 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?
Donor (Allogeneic) Hematopoietic Engraftment (time frame: Day 100 Following Hematopoietic Cell Transplant (HCT)). 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 Dec 2017.