NCT02427178

Brief Summary

The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. The stem cell transplant is called AHSCT (for "allogeneic hematopoetic stem cell transplantation"). The rare disease is called MNGIE (for "Mitochondrial NeuroGastroIntestinal Encephalomyopathy"). Patients with MNGIE will be transplanted with stem cells from an individual who is human leukocyte antigen (HLA) 10/10 matched. The purpose of the transplant is the production of thymidine phosphorylase.

Trial Health

15
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Mar 2015

Longer than P75 for phase_1

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2015

Completed
19 days until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

April 27, 2015

Completed
7.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2022

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2023

Completed
Last Updated

August 1, 2022

Status Verified

July 1, 2022

Enrollment Period

7.3 years

First QC Date

February 10, 2015

Last Update Submit

July 28, 2022

Conditions

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

Keywords

Allogeneic Hematopoietic Stem Cell TransplantationMNGIEStem Cell transplant

Outcome Measures

Primary Outcomes (1)

  • neutrophil count (cells/L)

    engraftment success

    42 days

Secondary Outcomes (4)

  • number of patient survival days

    100 days

  • chimerism percentage

    100 days

  • micromole/l dUrd

    100 days

  • micromole Thd

    100 days

Study Arms (1)

Open label

EXPERIMENTAL

Hematopoietic allogeneic stem cells will be transplanted: HLA testing will be performed on potential stem cell donors. HLA 10/10 matched donors are eligible, however there are additional criteria that will be applied to determine an acceptable donor. Patients will receive 2 X10 6 CD34 cells/kg weight.

Biological: Hematopoietic Allogeneic Stem Cells

Interventions

Hematopoietic Allogeneic Stem CellsBIOLOGICAL

HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).

Open label

Eligibility Criteria

Age5 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Homozygous or compound heterozygous mutations in the TYMP gene
  • Plasma thymidine level \>3micromole/L
  • Plasma deoxyuridine \>7.5 micromole/L
  • to 55 years of age
  • Appropriate stem cell donor (HLA 10/10 matched)
  • Karnofsky performance of at least 55

You may not qualify if:

  • Severe cognitive impairment
  • Severe psychiatric illness
  • Moderate to severe lung disease
  • Prior episode of peritonitis due to perforated diverticula
  • Prior episode of intestinal pseudo-obstruction
  • Moderate to severe hepatopathy
  • Moderate to severe diabetes Mellitus
  • Moderate to severe cardiomyopathy
  • Moderate to severe nephropathy
  • Pregnancy or planning to become pregnant during study
  • Hypersensitivity to E.coli derived products
  • HIV disease
  • Positive to anti-donor HLA DP

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (4)

  • Halter J, Schupbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krahenbuhl S, Lehmann T, Mandel H, Marti R, Mattle H, Orchard K, Savage D, Sue CM, Valcarcel D, Gratwohl A, Hirano M. Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant. 2011 Mar;46(3):330-337. doi: 10.1038/bmt.2010.100. Epub 2010 May 3.

    PMID: 20436523BACKGROUND

  • Marti R, Lopez LC, Hirano M. Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Methods Mol Biol. 2012;837:121-33. doi: 10.1007/978-1-61779-504-6_8.

    PMID: 22215544BACKGROUND

  • Hirano M, Nishino I, Nishigaki Y, Marti R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med. 2006;45(19):1103. doi: 10.2169/internalmedicine.45.6064. Epub 2006 Nov 1. No abstract available.

    PMID: 17077575BACKGROUND

  • Valentino ML, Marti R, Tadesse S, Lopez LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett. 2007 Jul 24;581(18):3410-4. doi: 10.1016/j.febslet.2007.06.042. Epub 2007 Jun 27.

    PMID: 17612528BACKGROUND

Study Officials

  • Michio Hirano, MD

    Columbia University

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Neurology

Study Record Dates

First Submitted

February 10, 2015

First Posted

April 27, 2015

Study Start

March 1, 2015

Primary Completion

June 1, 2022

Study Completion

June 1, 2023

Last Updated

August 1, 2022

Record last verified: 2022-07

Data Sharing

IPD Sharing
Will share

When applicable, we will submit a manuscript describing the results