MT2014-14 IT-MSC for Advanced Cerebral Adrenoleukodystrophy (cALD)
Primary Purpose
Cerebral Adrenoleukodystrophy
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Mesenchymal Stem Cells
Sponsored by
About this trial
This is an interventional treatment trial for Cerebral Adrenoleukodystrophy focused on measuring Cerebral Adrenoleukodystrophy, cALD
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 4 years at time of study enrollment
- Diagnosis of ALD - the diagnosis of ALD can be made by either biochemical or molecular/genetic evidence (plasma VLCFA or ABCD1 mutation analysis) supportive of ALD as the cause of cerebral demyelination
- Evidence of active cerebral disease - defined as the presence of gadolinium enhancement on a single brain MRI study - MRI used for eligibility determination may be performed at an outside institution; the most recent MRI used to determine eligibility must be within 2 calendar months of the date of enrollment on this study
- ALD MRI (Loes) score ≥ 10
- Off of N-acetylcysteine, systemic immunosuppressive drugs or any other therapeutic intervention (except hydrocortisone and/or fludracortisone for the treatment of adrenal insufficiency) for ≥ 10 days prior to the first IT-MSC dose
- Life expectancy of >6 months as determined by the enrolling researcher and documented in the medical record
- Voluntary written consent provided by parent(s)/guardian(s)
Exclusion Criteria:
- A candidate for allogeneic hematopoietic stem cell transplantation as determined by the University of Minnesota Inherited Metabolic and Storage Disease group
- Inability to undergo sedation, lumbar puncture or MRI studies for any reason
- Inability to stay in Minnesota for therapy through the day 28 evaluation
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Mesenchymal Stem Cell
Arm Description
Third party donor Mesenchymal Stem Cells (MSC) will be administered via intrathecal administration at the assigned dose on days 0, 7 and 14. Dose escalation will be guided by a fast track design. One patient is entered per dose level until a DLT is experienced. At that point, two additional patients will be enrolled at the same dose level. Dose levels will be 2.5 x 10e6 MSC/kg per dose, 5 x 10e6 MSC/kg per dose or 7.5 x 10e6 MSC/kg per dose.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose
Determine the maximum tolerated dose (MTD) of intrathecally-administered allogeneic, third-party mesenchymal stem cells (IT-MSC) in patients with active, advanced cerebral adrenoleukodystrophy (cALD).
Secondary Outcome Measures
Radiographic Response
Evaluate the incidence of, and time to, radiographic response in patients receiving IT-MSC for active, advanced cerebral adrenoleukodystrophy. Radiographic response is defined as the resolution of intravenous gadolinium contrast enhancement on brain MRI, or the absence of an increase in Loes score between the enrollment MRI and 6 month MRI.
Full Information
NCT ID
NCT02410239
First Posted
March 27, 2015
Last Updated
November 29, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02410239
Brief Title
MT2014-14 IT-MSC for Advanced Cerebral Adrenoleukodystrophy (cALD)
Official Title
MT2014-14 Intrathecal Administration of Mesenchymal Stem Cells (IT-MSC) for the Treatment of Advanced Cerebral Adrenoleukodystrophy (cALD)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Research cancelled
Study Start Date
June 2015 (Anticipated)
Primary Completion Date
July 2017 (Anticipated)
Study Completion Date
July 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the maximum tolerated dose (MTD) of mesenchymal stem cells (IT-MSC) in patients with active, advanced cerebral adrenoleukodystrophy (cALD).
Detailed Description
This is a single-institution dose escalation study to determine the maximum tolerated dose (MTD) of intrathecally administered allogeneic, 3rd party mesenchymal stem cells (IT-MSC) in patients with active, advanced cerebral adrenoleukodystrophy (cALD).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Adrenoleukodystrophy
Keywords
Cerebral Adrenoleukodystrophy, cALD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mesenchymal Stem Cell
Arm Type
Experimental
Arm Description
Third party donor Mesenchymal Stem Cells (MSC) will be administered via intrathecal administration at the assigned dose on days 0, 7 and 14. Dose escalation will be guided by a fast track design. One patient is entered per dose level until a DLT is experienced. At that point, two additional patients will be enrolled at the same dose level. Dose levels will be 2.5 x 10e6 MSC/kg per dose, 5 x 10e6 MSC/kg per dose or 7.5 x 10e6 MSC/kg per dose.
Intervention Type
Biological
Intervention Name(s)
Mesenchymal Stem Cells
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
Determine the maximum tolerated dose (MTD) of intrathecally-administered allogeneic, third-party mesenchymal stem cells (IT-MSC) in patients with active, advanced cerebral adrenoleukodystrophy (cALD).
Time Frame
Day 28 post intrathecal injection of MSC
Secondary Outcome Measure Information:
Title
Radiographic Response
Description
Evaluate the incidence of, and time to, radiographic response in patients receiving IT-MSC for active, advanced cerebral adrenoleukodystrophy. Radiographic response is defined as the resolution of intravenous gadolinium contrast enhancement on brain MRI, or the absence of an increase in Loes score between the enrollment MRI and 6 month MRI.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 4 years at time of study enrollment
Diagnosis of ALD - the diagnosis of ALD can be made by either biochemical or molecular/genetic evidence (plasma VLCFA or ABCD1 mutation analysis) supportive of ALD as the cause of cerebral demyelination
Evidence of active cerebral disease - defined as the presence of gadolinium enhancement on a single brain MRI study - MRI used for eligibility determination may be performed at an outside institution; the most recent MRI used to determine eligibility must be within 2 calendar months of the date of enrollment on this study
ALD MRI (Loes) score ≥ 10
Off of N-acetylcysteine, systemic immunosuppressive drugs or any other therapeutic intervention (except hydrocortisone and/or fludracortisone for the treatment of adrenal insufficiency) for ≥ 10 days prior to the first IT-MSC dose
Life expectancy of >6 months as determined by the enrolling researcher and documented in the medical record
Voluntary written consent provided by parent(s)/guardian(s)
Exclusion Criteria:
A candidate for allogeneic hematopoietic stem cell transplantation as determined by the University of Minnesota Inherited Metabolic and Storage Disease group
Inability to undergo sedation, lumbar puncture or MRI studies for any reason
Inability to stay in Minnesota for therapy through the day 28 evaluation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Orchard, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
MT2014-14 IT-MSC for Advanced Cerebral Adrenoleukodystrophy (cALD)
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