MT2014-14 IT-MSC for Advanced Cerebral Adrenoleukodystrophy (cALD)

Phase 1

Withdrawn

• Conditions: Cerebral Adrenoleukodystrophy
• Interventions: Biological: Mesenchymal Stem Cells

• Registration Number: NCT02410239
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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).

Study Timeline

• Study First Submitted: 2015-03-27
• Study First Submitted QC: 2015-04-01
• Study First Posted: 2015-04-07
• Study Start: 2015-06
• Primary Completion: 2017-07
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-29
• Last Update Posted: 2017-12-02
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mesenchymal Stem Cell	Mesenchymal Stem Cells	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.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	Day 28 post intrathecal injection of MSC	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

Name	Time	Method
Radiographic Response	6 months	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.