MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study (MASS)

This study is currently recruiting participants.

See

Contacts and Locations

Verified January 2017 by Michio Hirano, Columbia University

Sponsor:

Collaborators:

Cornell University

National Institute of Neurological Disorders and Stroke (NINDS)

Information provided by (Responsible Party):

Michio Hirano, Columbia University

ClinicalTrials.gov Identifier:

NCT02427178

First received: February 10, 2015

Last updated: January 25, 2017

Last verified: January 2017

History of Changes

Purpose

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.

Condition	Intervention	Phase
Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)	Biological: Hematopoietic Allogeneic Stem Cells	Phase 1


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study

Resource links provided by NLM:

Genetics Home Reference related topics: mitochondrial neurogastrointestinal encephalopathy disease

Genetic and Rare Diseases Information Center resources: Encephalomyopathy Mitochondrial Neurogastrointestinal Encephalopathy Syndrome

U.S. FDA Resources

Further study details as provided by Michio Hirano, Columbia University:

Primary Outcome Measures:

neutrophil count (cells/L) [ Time Frame: 42 days ]
engraftment success

Secondary Outcome Measures:

number of patient survival days [ Time Frame: 100 days ]
is the patient al
chimerism percentage [ Time Frame: 100 days ]
percent of donor cell chimerism at 100 days
micromole/l dUrd [ Time Frame: 100 days ]
level of deoxyuridine
micromole Thd [ Time Frame: 100 days ]
level of thymidine


Estimated Enrollment:	12
Study Start Date:	March 2015
Estimated Study Completion Date:	June 2023
Estimated Primary Completion Date:	June 2022 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Open label 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 HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).

Detailed Description:

Patients who have been identified as having MNGIE by genetic testing and/or reduced thymidine phosphorylase levels will be considered for this study. The study team physician will evaluate the condition of the patient and determine if they are eligible. An HLA matched donor is necessary for transplantation. If a suitable donor is found the transplant process can proceed. The patient receives immunosuppressive therapy ( 1 week in the hospital) with subsequent IV transfer of stem cells from the donor. The patient remains in the hospital for approximately 1 month to monitor the transplant. The patient is required to attend research visits at days 0, 100, 6m, 18m and 24 m.

Eligibility


Ages Eligible for Study:	5 Years to 55 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02427178

Contacts


Contact: Kris Engelstad, MS CGC	1-212-305-6834	ke4@cumc.columbia.edu

Locations


United States, New York
Columbia University	Recruiting
New York City, New York, United States, 10032
Contact: Michio Hirano, MD 212-305-1048 mh29@cumc.columbia.edu
Contact: Kris Engelstad, MS CGC 1-212-305-6834 ke4@cumc.columbia.edu
Sub-Investigator: Johnston Grier, BS

Sponsors and Collaborators

Michio Hirano

Cornell University

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators


Principal Investigator:	Michio Hirano, MD	Columbia University

More Information

Publications:

Halter J, Schüpbach WM, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krähenbühl 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):330-7. doi: 10.1038/bmt.2010.100. Epub 2010 May 3.

Martí R, López 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.

Hirano M, Nishino I, Nishigaki Y, Martí R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med. 2006;45(19):1103. Epub 2006 Nov 1.

Valentino ML, Martí R, Tadesse S, López 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. Epub 2007 Jun 27.


Responsible Party:	Michio Hirano, Professor of Neurology, Columbia University
ClinicalTrials.gov Identifier:	NCT02427178 History of Changes
Obsolete Identifiers:	NCT02363881
Other Study ID Numbers:	AAAI1718 U54NS078059 ( U.S. NIH Grant/Contract )
Study First Received:	February 10, 2015
Last Updated:	January 25, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	When applicable, we will submit a manuscript describing the results

Keywords provided by Michio Hirano, Columbia University:


Allogeneic Hematopoietic Stem Cell Transplantation MNGIE Stem Cell transplant

ClinicalTrials.gov processed this record on July 14, 2017

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